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Familial melanoma v2.15 Ida Ertmanska List of related panels changed from R254 to R254; GT402; TP483
Familial melanoma v2.14 MITF Achchuthan Shanmugasundram Classified gene: MITF as Amber List (moderate evidence)
Familial melanoma v2.14 MITF Achchuthan Shanmugasundram Added comment: Comment on list classification: There is emerging evidence for significant enrichment of germline p.Glu318Lys variant from MITF gene in melanoma patients in comparison to population control. However, there are no other variants from this gene has been associated with risk of melanoma. This gene has been rated amber with current evidence.
Familial melanoma v2.14 MITF Achchuthan Shanmugasundram Gene: mitf has been classified as Amber List (Moderate Evidence).
Familial melanoma v2.13 MITF Achchuthan Shanmugasundram Phenotypes for gene: MITF were changed from Mucosal melanoma to {Melanoma, cutaneous malignant, susceptibility to, 8}, OMIM:614456; melanoma, cutaneous malignant, susceptibility to, 8, MONDO:0013759
Familial melanoma v2.12 MITF Achchuthan Shanmugasundram Publications for gene: MITF were set to PMID: 42177185
Familial melanoma v2.11 MITF Achchuthan Shanmugasundram Mode of inheritance for gene: MITF was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial melanoma v2.10 MITF Achchuthan Shanmugasundram changed review comment from: PMID:22012259 (2011) reported the presence of higher than five-fold increased risk of developing melanoma, renal cell carcinoma or both cancers in individuals with germline missense substitution in MITF gene (p.Glu318Lys), when compared with controls.

PMID: 22080950 (2011) reported the whole-genome sequencing of probands from several melanoma families, of which one individual was identified with p.Glu318Lys variant in MITF gene. The MITF variant allele was found in 3/7 melanoma cases assessed in this family, consistent with it being a medium-penetrance melanoma risk variant. This variant was significantly associated with melanoma in a large Australian case-control sample and in an independent case-control sample from the UK. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets.

PMID:42177185 (2026) reported a study of 346 mucosal melanoma patients, of which germline pathogenic variant in MITF (p.Glu318Lys) was identified in six patients, which was a significant enrichment compared to population control rates.

This gene has been associated with relevant susceptibility phenotype in OMIM (MIM #614456) and OMIm record was last accessed 19 June 2026.; to: PMID:22012259 (2011) reported the presence of higher than five-fold increased risk of developing melanoma, renal cell carcinoma or both cancers in individuals with germline missense substitution in MITF gene (p.Glu318Lys), when compared with controls.

PMID: 22080950 (2011) reported the whole-genome sequencing of probands from several melanoma families, of which one individual was identified with p.Glu318Lys variant in MITF gene. The MITF variant allele was found in 3/7 melanoma cases assessed in this family, consistent with it being a medium-penetrance melanoma risk variant. This variant was significantly associated with melanoma in a large Australian case-control sample and in an independent case-control sample from the UK. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets.

PMID:42177185 (2026) reported a study of 346 mucosal melanoma patients, of which germline pathogenic variant in MITF (p.Glu318Lys) was identified in six patients, which was a significant enrichment compared to population control rates.

This gene has been associated with relevant susceptibility phenotype in OMIM (MIM #614456) and OMIM record was last accessed 19 June 2026. This gene is included in Cancer panel with 'limited' rating in Gene2Phenotype.
Familial melanoma v2.10 MITF Achchuthan Shanmugasundram changed review comment from: PMID:22012259 (2011) reported the presence of higher than five-fold increased risk of developing melanoma, renal cell carcinoma or both cancers in individuals with germline missense substitution in MITF gene (p.Glu318Lys), when compared with controls.

PMID: 22080950 (2011) reported the whole-genome sequencing of probands from several melanoma families, of which one individual was identified with p.Glu318Lys variant in MITF gene. The MITF variant allele was found in 3/7 melanoma cases assessed in this family, consistent with it being a medium-penetrance melanoma risk variant. This variant was significantly associated with melanoma in a large Australian case-control sample and in an independent case-control sample from the UK. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets. ; to: PMID:22012259 (2011) reported the presence of higher than five-fold increased risk of developing melanoma, renal cell carcinoma or both cancers in individuals with germline missense substitution in MITF gene (p.Glu318Lys), when compared with controls.

PMID: 22080950 (2011) reported the whole-genome sequencing of probands from several melanoma families, of which one individual was identified with p.Glu318Lys variant in MITF gene. The MITF variant allele was found in 3/7 melanoma cases assessed in this family, consistent with it being a medium-penetrance melanoma risk variant. This variant was significantly associated with melanoma in a large Australian case-control sample and in an independent case-control sample from the UK. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets.

PMID:42177185 (2026) reported a study of 346 mucosal melanoma patients, of which germline pathogenic variant in MITF (p.Glu318Lys) was identified in six patients, which was a significant enrichment compared to population control rates.

This gene has been associated with relevant susceptibility phenotype in OMIM (MIM #614456) and OMIm record was last accessed 19 June 2026.
Familial melanoma v2.10 MITF Achchuthan Shanmugasundram edited their review of gene: MITF: Changed publications to: 22012259, 22080950, 42177185
Familial melanoma v2.10 MITF Achchuthan Shanmugasundram changed review comment from: PMID:22012259 (2011) reported the presence of higher than five-fold increased risk of developing melanoma, renal cell carcinoma or both cancers in individuals with germline missense substitution in MITF gene (p.Glu318Lys), when compared with controls.

PMID: 22080950 (2011) reported the whole-genome sequencing of probands from several melanoma families, of which one individual was identified with p.Glu318Lys variant in MITF gene.; to: PMID:22012259 (2011) reported the presence of higher than five-fold increased risk of developing melanoma, renal cell carcinoma or both cancers in individuals with germline missense substitution in MITF gene (p.Glu318Lys), when compared with controls.

PMID: 22080950 (2011) reported the whole-genome sequencing of probands from several melanoma families, of which one individual was identified with p.Glu318Lys variant in MITF gene. The MITF variant allele was found in 3/7 melanoma cases assessed in this family, consistent with it being a medium-penetrance melanoma risk variant. This variant was significantly associated with melanoma in a large Australian case-control sample and in an independent case-control sample from the UK. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets.
Familial melanoma v2.10 MITF Achchuthan Shanmugasundram reviewed gene: MITF: Rating: AMBER; Mode of pathogenicity: None; Publications: 22012259, 22080950; Phenotypes: {Melanoma, cutaneous malignant, susceptibility to, 8}, OMIM:614456, melanoma, cutaneous malignant, susceptibility to, 8, MONDO:0013759; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial melanoma v2.10 CHEK2 Ida Ertmanska Classified gene: CHEK2 as Amber List (moderate evidence)
Familial melanoma v2.10 CHEK2 Ida Ertmanska Added comment: Comment on list classification: While there is emerging evidence for association of CHEK2 variants with risk of melanoma (e.g., PMID: 42177185), there are several studies that did not find a significant association. Hence, this gene can only be rated Amber with the current evidence.
Familial melanoma v2.10 CHEK2 Ida Ertmanska Gene: chek2 has been classified as Amber List (Moderate Evidence).
Familial melanoma v2.9 CHEK2 Ida Ertmanska Phenotypes for gene: CHEK2 were changed from Tumor predisposition syndrome 4, breast/prostate/colorectal, OMIM:609265 to Tumor predisposition syndrome 4, breast/prostate/colorectal, OMIM:609265; mucosal melanoma, MONDO:0000544; uveal melanoma, MONDO:0006486
Familial melanoma v2.8 CHEK2 Ida Ertmanska Phenotypes for gene: CHEK2 were changed from Mucosal melanoma to Tumor predisposition syndrome 4, breast/prostate/colorectal, OMIM:609265
Familial melanoma v2.7 CHEK2 Ida Ertmanska Publications for gene: CHEK2 were set to PMID: 42177185
Familial melanoma v2.6 CHEK2 Ida Ertmanska Mode of inheritance for gene: CHEK2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial melanoma v2.5 CHEK2 Ida Ertmanska reviewed gene: CHEK2: Rating: AMBER; Mode of pathogenicity: None; Publications: 32531112, 40283643; Phenotypes: Tumor predisposition syndrome 4, breast/prostate/colorectal, OMIM:609265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial melanoma v2.5 CHEK2 Riyaad Aungraheeta gene: CHEK2 was added
gene: CHEK2 was added to Familial melanoma. Sources: Literature
Mode of inheritance for gene: CHEK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CHEK2 were set to PMID: 42177185
Phenotypes for gene: CHEK2 were set to Mucosal melanoma
Review for gene: CHEK2 was set to AMBER
Added comment: The CHEK2 c.1100delC variant was enriched in this retrospective cohort of mucosal melanoma patients compared to population controls (OR 6.7; 95% CI 1.8–17.5).
Sources: Literature
Familial melanoma v2.5 MITF Riyaad Aungraheeta gene: MITF was added
gene: MITF was added to Familial melanoma. Sources: Literature
Mode of inheritance for gene: MITF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MITF were set to PMID: 42177185
Phenotypes for gene: MITF were set to Mucosal melanoma
Review for gene: MITF was set to AMBER
Added comment: The MITF E318K variant was enriched in this retrospective cohort of mucosal melanoma patients compared to population controls (OR 6.0; 95% CI 2.2–13.2).
Sources: Literature
Familial melanoma v2.4 BAP1 Arina Puzriakova Phenotypes for gene: BAP1 were changed from to Tumor predisposition syndrome 1, OMIM:614327; {Uveal melanoma, susceptibility to, 2}, OMIM:606661
Familial melanoma v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Familial melanoma v2.0 Catherine Snow promoted panel to version 2.0
Familial melanoma v1.14 TERT Arina Puzriakova Publications for gene: TERT were set to 23348503
Familial melanoma v1.13 TERT Arina Puzriakova Tag watchlist tag was added to gene: TERT.
Familial melanoma v1.13 TERT Arina Puzriakova reviewed gene: TERT: Rating: ; Mode of pathogenicity: None; Publications: 23348503, 23348506, 35912549; Phenotypes: {Melanoma, cutaneous malignant, 9}, OMIM:615134; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial melanoma v1.13 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from to {Melanoma, cutaneous malignant, 9}, OMIM:615134
Familial melanoma v1.12 POT1 Arina Puzriakova Tag for-review was removed from gene: POT1.
Familial melanoma v1.12 POT1 Arina Puzriakova commented on gene: POT1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Familial melanoma v1.11 POT1 Arina Puzriakova Source Expert Review Green was added to POT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Familial melanoma v1.10 CDKN2A Arina Puzriakova Phenotypes for gene: CDKN2A were changed from to {Melanoma, cutaneous malignant, 2}, OMIM:155601; {Melanoma and neural system tumor syndrome}, OMIM:155755; {Melanoma-pancreatic cancer syndrome}, OMIM:606719
Familial melanoma v1.9 POT1 Arina Puzriakova Phenotypes for gene: POT1 were changed from Melanoma, cutaneous malignant, susceptibility to, 10, 615848 to Melanoma, cutaneous malignant, susceptibility to, 10, OMIM:615848
Familial melanoma v1.8 POT1 Arina Puzriakova Publications for gene: POT1 were set to 24686849; 24686846; 29523635; 30451293; 30586141; 32325837
Familial melanoma v1.7 POT1 Arina Puzriakova edited their review of gene: POT1: Changed publications: 24686849, 24686846, 29523635, 30451293, 30586141, 32325837, 32907878
Familial melanoma v1.7 POT1 Arina Puzriakova Tag for-review tag was added to gene: POT1.
Familial melanoma v1.7 POT1 Arina Puzriakova Phenotypes for gene: POT1 were changed from to Melanoma, cutaneous malignant, susceptibility to, 10, 615848
Familial melanoma v1.6 POT1 Arina Puzriakova Publications for gene: POT1 were set to
Familial melanoma v1.5 POT1 Arina Puzriakova Classified gene: POT1 as Amber List (moderate evidence)
Familial melanoma v1.5 POT1 Arina Puzriakova Added comment: Comment on list classification: Based on evidence provided by several publications, POT1 should be considered for a rating upgrade from Amber to Green, and therefore will be flagged for review at the date of next GMS panel update (added 'for-review' tag).
Familial melanoma v1.5 POT1 Arina Puzriakova Gene: pot1 has been classified as Amber List (Moderate Evidence).
Familial melanoma v1.4 POT1 Arina Puzriakova edited their review of gene: POT1: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial melanoma v1.4 POT1 Arina Puzriakova reviewed gene: POT1: Rating: ; Mode of pathogenicity: None; Publications: 24686849, 24686846, 29523635, 30451293, 30586141, 32325837; Phenotypes: Melanoma, cutaneous malignant, susceptibility to, 10, 615848; Mode of inheritance: None
Familial melanoma v1.3 Catherine Snow Panel version has been signed off
Familial melanoma v1.0 Ivone Leong promoted panel to version 1.0
Familial melanoma v0.24 Ivone Leong Panel types changed to GMS Rare Disease; GMS signed-off
Familial melanoma v0.23 TERF2IP Ivone Leong commented on gene: TERF2IP
Familial melanoma v0.23 BRCA2 Ivone Leong commented on gene: BRCA2
Familial melanoma v0.23 ACD Ivone Leong changed review comment from: Comment on list classification: As discussed in the GMS Inherited Cancer Specialist Test Group webex call 31st Jan 2019: The Specialist Test Group agreed that this gene should be rated amber.; to: As discussed in the GMS Inherited Cancer Specialist Test Group webex call 31st Jan 2019: The Specialist Test Group agreed that this gene should be rated amber.
Familial melanoma v0.23 ACD Ivone Leong commented on gene: ACD
Familial melanoma v0.23 CDKN2A Ivone Leong commented on gene: CDKN2A
Familial melanoma v0.23 CDK4 Ivone Leong commented on gene: CDK4
Familial melanoma v0.23 BAP1 Ivone Leong commented on gene: BAP1
Familial melanoma v0.23 Ivone Leong List of related panels changed from to R254
Familial melanoma v0.22 TERT Ivone Leong Publications for gene: TERT were set to
Familial melanoma v0.21 TERT Ivone Leong Classified gene: TERT as Amber List (moderate evidence)
Familial melanoma v0.21 TERT Ivone Leong Added comment: Comment on list classification: As discussed in the GMS Inherited Cancer Specialist Test Group webex call 31st Jan 2019: The Specialist Test Group agreed that this gene should be rated amber.
Familial melanoma v0.21 TERT Ivone Leong Gene: tert has been classified as Amber List (Moderate Evidence).
Familial melanoma v0.20 POT1 Ivone Leong Classified gene: POT1 as Amber List (moderate evidence)
Familial melanoma v0.20 POT1 Ivone Leong Added comment: Comment on list classification: As discussed in the GMS Inherited Cancer Specialist Test Group webex call 31st Jan 2019: The Specialist Test Group agreed that this gene should be rated amber.
Familial melanoma v0.20 POT1 Ivone Leong Gene: pot1 has been classified as Amber List (Moderate Evidence).
Familial melanoma v0.19 TERT Ivone Leong Classified gene: TERT as Amber List (moderate evidence)
Familial melanoma v0.19 TERT Ivone Leong Gene: tert has been classified as Amber List (Moderate Evidence).
Familial melanoma v0.18 POT1 Ivone Leong Classified gene: POT1 as Amber List (moderate evidence)
Familial melanoma v0.18 POT1 Ivone Leong Gene: pot1 has been classified as Amber List (Moderate Evidence).
Familial melanoma v0.17 TERT Ivone Leong Mode of inheritance for gene: TERT was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial melanoma v0.16 POT1 Ivone Leong Mode of inheritance for gene: POT1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial melanoma v0.15 BRCA2 Ivone Leong Mode of inheritance for gene: BRCA2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial melanoma v0.14 ACD Ivone Leong Mode of inheritance for gene: ACD was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial melanoma v0.13 CDKN2A Ivone Leong Mode of inheritance for gene: CDKN2A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial melanoma v0.12 CDK4 Ivone Leong Mode of inheritance for gene: CDK4 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial melanoma v0.11 BAP1 Ivone Leong Mode of inheritance for gene: BAP1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial melanoma v0.9 TERF2IP Ivone Leong Classified gene: TERF2IP as Amber List (moderate evidence)
Familial melanoma v0.9 TERF2IP Ivone Leong Gene: terf2ip has been classified as Amber List (Moderate Evidence).
Familial melanoma v0.8 CDKN2A Ivone Leong Classified gene: CDKN2A as Green List (high evidence)
Familial melanoma v0.8 CDKN2A Ivone Leong Gene: cdkn2a has been classified as Green List (High Evidence).
Familial melanoma v0.7 CDK4 Ivone Leong Classified gene: CDK4 as Green List (high evidence)
Familial melanoma v0.7 CDK4 Ivone Leong Gene: cdk4 has been classified as Green List (High Evidence).
Familial melanoma v0.6 BRCA2 Ivone Leong Classified gene: BRCA2 as Amber List (moderate evidence)
Familial melanoma v0.6 BRCA2 Ivone Leong Gene: brca2 has been classified as Amber List (Moderate Evidence).
Familial melanoma v0.5 BAP1 Ivone Leong Classified gene: BAP1 as Green List (high evidence)
Familial melanoma v0.5 BAP1 Ivone Leong Gene: bap1 has been classified as Green List (High Evidence).
Familial melanoma v0.4 ACD Ivone Leong Classified gene: ACD as Amber List (moderate evidence)
Familial melanoma v0.4 ACD Ivone Leong Gene: acd has been classified as Amber List (Moderate Evidence).
Familial melanoma v0.3 POT1 Rachel Robinson reviewed gene: POT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial melanoma v0.3 TERT Rachel Robinson reviewed gene: TERT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial melanoma v0.3 CDK4 Rachel Robinson reviewed gene: CDK4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial melanoma v0.3 CDKN2A Rachel Robinson reviewed gene: CDKN2A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial melanoma v0.3 BAP1 Rachel Robinson reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial melanoma v0.3 BRCA2 Lara Hawkes reviewed gene: BRCA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Familial melanoma v0.3 POT1 Lara Hawkes reviewed gene: POT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Familial melanoma v0.3 ACD Lara Hawkes reviewed gene: ACD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Familial melanoma v0.3 TERF2IP Lara Hawkes reviewed gene: TERF2IP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Familial melanoma v0.3 TERT Lara Hawkes reviewed gene: TERT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Familial melanoma v0.3 CDKN2A Lara Hawkes reviewed gene: CDKN2A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Familial melanoma v0.3 CDK4 Lara Hawkes reviewed gene: CDK4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Familial melanoma v0.3 BAP1 Lara Hawkes reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Familial melanoma v0.2 BRCA2 Ivone Leong gene: BRCA2 was added
gene: BRCA2 was added to Familial melanoma. Sources: NHS GMS
Mode of inheritance for gene: BRCA2 was set to
Familial melanoma v0.2 POT1 Ivone Leong gene: POT1 was added
gene: POT1 was added to Familial melanoma. Sources: Expert List,NHS GMS
Mode of inheritance for gene: POT1 was set to
Familial melanoma v0.2 ACD Ivone Leong gene: ACD was added
gene: ACD was added to Familial melanoma. Sources: NHS GMS
Mode of inheritance for gene: ACD was set to
Familial melanoma v0.2 TERF2IP Ivone Leong gene: TERF2IP was added
gene: TERF2IP was added to Familial melanoma. Sources: NHS GMS
Mode of inheritance for gene: TERF2IP was set to
Familial melanoma v0.2 TERT Ivone Leong gene: TERT was added
gene: TERT was added to Familial melanoma. Sources: Expert List,NHS GMS
Mode of inheritance for gene: TERT was set to
Familial melanoma v0.2 CDKN2A Ivone Leong gene: CDKN2A was added
gene: CDKN2A was added to Familial melanoma. Sources: Expert List,NHS GMS
Mode of inheritance for gene: CDKN2A was set to
Familial melanoma v0.2 CDK4 Ivone Leong gene: CDK4 was added
gene: CDK4 was added to Familial melanoma. Sources: Expert List,NHS GMS
Mode of inheritance for gene: CDK4 was set to
Familial melanoma v0.2 BAP1 Ivone Leong gene: BAP1 was added
gene: BAP1 was added to Familial melanoma. Sources: Expert List,NHS GMS
Mode of inheritance for gene: BAP1 was set to
Familial melanoma v0.0 Ellen McDonagh Added Panel Familial melanoma
Set panel types to: GMS Rare Disease