Submissions for variant NM_005379.4(MYO1A):c.2872A>G (p.Ser958Gly)

gnomAD frequency: 0.00009  dbSNP: rs184810732

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151433	SCV000199460	uncertain significance	not specified	2013-04-10	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Ser958Gly varia nt in MYO1A has not been reported in individuals affected with hearing loss, but has been identified in 3/340 (0.9%) of Chinese chromosomes by the 1000 Genomes Project (dbSNP rs184810732). Although this variant has been seen in the general population, the sample size is too small to rule out a pathogenic role. Computa tional analyses (biochemical amino acid properties, conservation, AlignGVGD, Pol yPhen2, and SIFT) suggest that the Ser958Gly variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant cannot be determined with cer tainty; however, based upon its presence in the 1000 Genome database and the com putational assessment, we lean towards a more likely benign role.
Eurofins Ntd Llc (ga)	RCV000726841	SCV000703582	uncertain significance	not provided	2016-12-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003975179	SCV004787517	likely benign	MYO1A-related disorder	2019-03-28	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).