Submissions for variant NM_016239.4(MYO15A):c.8269G>A (p.Val2757Met)

gnomAD frequency: 0.00139  dbSNP: rs140140417

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151415	SCV000199430	benign	not specified	2016-01-15	criteria provided, single submitter	clinical testing	p.Val2757Met in exon 46 of MYO15A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, hedgehog, elephant, hyrax and platypus have a methionine (Met) at this position despite high nearby amino acid conservation. In addition, this variant has been identified in 0.6% (94/16282) of South Asian chromosomes including 1 ho mozygote by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs140140417).
Illumina Laboratory Services, Illumina	RCV000289377	SCV000401197	uncertain significance	Autosomal recessive nonsyndromic hearing loss 3	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000762238	SCV000717973	benign	not provided	2019-04-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000762238	SCV000892522	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	MYO15A: BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV000762238	SCV001031540	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000289377	SCV002047772	benign	Autosomal recessive nonsyndromic hearing loss 3	2021-07-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927460	SCV004741694	likely benign	MYO15A-related disorder	2020-03-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).