Hereditary neuropathy or pain disorder
Gene: MYH14
The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 6:06 p.m. | Last Modified: 10 Oct 2023, 6:06 p.m.
Panel Version: 3.58
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Comment on list classification: There are four families reported with the same variant (p.Arg941Leu) and with supporting functional studies characterising this variant. As the reported cases came from both Korean and North American families, it is not likely to be a founder variant. Hence, this gene can be promoted to GREEN rating at the next GMS update.Created: 18 May 2023, 6:08 p.m. | Last Modified: 18 May 2023, 6:08 p.m.
Panel Version: 3.30
PMID:21480433 reported a large 5-generation Korean family identified with c.2822G>T/ p.Arg941Leu variant and presenting with complex phenotype including progressive peripheral neuropathy, distal myopathy, later onset of hoarseness and hearing loss.
PMID:27875632 reported a large 6-generation North American family with the same variant and presenting with distal hereditary motor neuropathy, atrophy and hearing loss.
PMID:31231018 reported a 3-generation Canadian family with the same variant and presenting with peripheral neuropathy manifesting in 2nd and 3rd decades of life, and sensorineural hearing loss manifesting in early childhood. It also provides functional evidence on the reported variant, which impairs non-muscle myosin protein function.
PMID:35274842 reported a second Korean family with the same variant and the phenotypes are similar to the first Korean family.Created: 18 May 2023, 6:02 p.m. | Last Modified: 18 May 2023, 6:02 p.m.
Panel Version: 3.27
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, OMIM:614369
Publications
Third extended family with the same missense variant Arg941Leu is now reported in 31231018 (in addition to two families in 21480433 and 27875632), with additional new functional evidence. The variant is NOT present in gnomAD. Therefore, enough evidence for the green rating.Created: 8 Jan 2023, 12:39 p.m. | Last Modified: 8 Jan 2023, 12:39 p.m.
Panel Version: 2.7
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Neuropathy
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - minor feature / Hearing loss enough evidence for Green; 1 family with hearing loss & neuropathy in literature, are there additional unpublished families?Created: 6 Dec 2019, 9:10 p.m. | Last Modified: 6 Dec 2019, 9:10 p.m.
Panel Version: 0.82
Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.Created: 6 Dec 2019, 9:09 p.m. | Last Modified: 6 Dec 2019, 9:09 p.m.
Panel Version: 0.82
Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.Created: 29 Apr 2019, 12:53 p.m.
More evidence needed. PMID:21480433 and PMID: 27875632 - discount as dominant gene and variant far too common on gnomAD. PMID: 30373780 - 2 probands but one had pathogenic variant in another gene. No further evidenceCreated: 29 Apr 2019, 12:30 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, 614369
Publications
2 large families with novel mutation (not on GNOMAD). Both deafness and neuropathy. Gene already on deafness panelCreated: 16 May 2019, 9:43 p.m.
Single familyCreated: 9 Dec 2015, 8:50 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Single familyCreated: 8 Dec 2015, 3:07 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag Q2_23_promote_green was removed from gene: MYH14.
Source Expert Review Green was added to MYH14. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_23_promote_green tag was added to gene: MYH14.
Gene: myh14 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MYH14 were changed from ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, 614369 to ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, OMIM:614369
Publications for gene: MYH14 were set to 30373780; 21480433; 27875632
Gene: myh14 has been classified as Amber List (Moderate Evidence).
gene: MYH14 was added gene: MYH14 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,South West GLH,Expert Review Red,Expert Review Mode of inheritance for gene: MYH14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MYH14 were set to 30373780; 21480433; 27875632 Phenotypes for gene: MYH14 were set to ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, 614369