Hypertrophic cardiomyopathy - teen and adult
Gene: JPH2
Assessed as MODERATE evidence for gene-disease association by ClinGen.
Conflicting evidence for missense variants in particular: one of the variants p.Gly505Ser is present in >500 individuals in gnomad, including 7 homozygotes, and another novel missense variant was observed in an 86-year-old man, diagnosed with hypertrophic cardiomyopathy, in whom echocardiography and cardiac magnetic resonance imaging strongly suggested amyloidosis to be the underlying cause.Created: 14 Oct 2020, 3:49 a.m. | Last Modified: 14 Oct 2020, 3:49 a.m.
Panel Version: 2.11
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Cardiomyopathy, hypertrophic, MIM#613873
Publications
As a result of watchlist tag audit the watchlist tag was removed from JPH2- this is now a green gene with sufficient evidence/reviewCreated: 13 Jan 2020, 3:31 p.m. | Last Modified: 13 Jan 2020, 3:31 p.m.
Panel Version: 2.1
Submitted on behalf of the GMS Cardiology specialist group. This gene did not achieve a consensus Green rating; however, the group agreed that the existing evidence (published and in-house data) was sufficient to support inclusion in this panel.Created: 9 Dec 2019, 1:19 p.m. | Last Modified: 9 Dec 2019, 1:19 p.m.
Panel Version: 1.93
Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.Created: 2 Dec 2019, 11:26 a.m. | Last Modified: 2 Dec 2019, 11:26 a.m.
Panel Version: 1.81
Gene not currently tested on Manchester cardiac gene panel. 16 variants listed on HGMD (accessed 19/09/2019). ClinGen Knowledge Base: moderate association with hypertrophic cardiomyopathy 17 (accessed 19/09/2019).Created: 19 Sep 2019, 10:12 a.m. | Last Modified: 19 Sep 2019, 10:12 a.m.
Panel Version: 1.74
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Cardiomyopathy, hypertrophic, 17 (613873)
Publications
Cardiomyopathy, hypertrophic, 17 (605267 )Created: 25 Mar 2019, 4:30 p.m.
Weak evidence for primary role in pathogenicity: 28082330. Insufficient evidence, no supporting segregation, despite functional assays. PMID: 28393127 - a novel variant identified in a proband with significant basal septal hypertrophy. Neither parents were genotyped. his mutation was absent in 159,358 reference alleles. Variants in in MYH7, MYBPC3, MYL2, MYL3, TTNT2, TTNI3, TNNC1, TPM1, ACTC, PRKAG2, GLA, and LAMP2 genes, were excluded in this patient. Mice with this variant exhibit similar basal hypertrophy using a newly developed echo imaging plane, and this was confirmed using cardiac MRI. Histological analysis demonstrated cardiomyocyte hypertrophy and disarray consistent with HCM. 3 additional missense variants reported in 3 cases in PMID: 17509612 (2007), however another missense variant Gly550Ser in this gene has been reclassified as unknown pathogenic significance, due to presence in allele frequency databases. HGMD: 8 DM variants - 3 DCM rest HCM. Functional studies shown an effect in JPH2 but no variants with evidence of segregation. 10.1093/eurheartj/ehw603Created: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene on Royal Brompton diagnostic panel. Moderate evidence for association in PMID:Gene on Royal Brompton diagnostic panel. A Likely pathogenic variation with good segregation reported in our labCreated: 19 Mar 2019, 5:28 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.Created: 20 Feb 2019, 2:17 p.m.
PMID: 28393127 - a novel variant identified in a proband with significant basal septal hypertrophy. Neither parents wee genotyped. his mutation was absent in 159,358 reference alleles. Variants in in MYH7, MYBPC3, MYL2, MYL3, TTNT2, TTNI3, TNNC1, TPM1, ACTC, PRKAG2, GLA, and LAMP2 genes, were excluded in this patient. Mice with this variant exhibit similar basal hypertrophy using a newly developed echo imaging plane, and this was confirmed using cardiac MRI. Histological analysis demonstrated cardiomyocyte hypertrophy and disarray consistent with HCM. 3 additional missense variants reported in 3 cases in PMID: 17509612 (2007), however another missense variant Gly550Ser in this gene has been reclassified as unknown pathogenic significance, due to presence in allele frequency databases.Created: 14 Aug 2017, 1:37 p.m.
Publications
Tag watchlist was removed from gene: JPH2.
Source Expert Review Green was added to JPH2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: JPH2 were changed from Cardiomyopathy, familial hypertrophic 17, to Cardiomyopathy, familial hypertrophic 17 (613873)
Publications for gene: JPH2 were set to 28393127; 17509612; 17476457
Source South West GLH was added to JPH2. Mode of inheritance for gene JPH2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Source London South GLH was added to JPH2.
Publications for JPH2 were set to 28393127;17509612;17476457
JPH2 was added to Hypertrophic Cardiomyopathypanel. Sources: Expert list
JPH2 was added to Hypertrophic Cardiomyopathypanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
JPH2 was added to Hypertrophic Cardiomyopathypanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen