Submissions for variant NM_000260.4(MYO7A):c.640G>A (p.Gly214Arg)

gnomAD frequency: 0.00001  dbSNP: rs111033283

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036233	SCV000059885	pathogenic	Rare genetic deafness	2016-08-23	criteria provided, single submitter	clinical testing	The p.Gly214Arg variant in MYO7A has been reported in over 10 probands with Ushe r syndrome who were either homozygous for the variant or compound heterozygous w ith a second pathogenic or likely pathogenic variant in MYO7A (Adato 1997, Apari si 2013, Bujakowska 2014, Jaijo 2011, Jaijo 2009, Jaijo 2006, Le Quesne Stabej 2 012, Riazuddin 2008, Roux 2011, LMM data). It has not been identified in large p opulation studies. Computational prediction tools and conservation analyses sugg est that this variant may impact the protein. In summary, this variant meets our criteria to be classified as pathogenic for Usher syndrome in an autosomal rece ssive manner based on its presence in homozygosity or compound heterozygosity wi th a second pathogenic allele in many individuals with Usher syndrome, and low f requency in the general population.
Eurofins Ntd Llc (ga)	RCV000724325	SCV000232036	pathogenic	not provided	2014-10-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000515404	SCV000611217	pathogenic	Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2021-07-29	criteria provided, single submitter	clinical testing
Invitae	RCV000724325	SCV000962274	pathogenic	not provided	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 214 of the MYO7A protein (p.Gly214Arg). This variant is present in population databases (rs111033283, gnomAD 0.006%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 9382091, 16470552, 20497194, 24199935, 26969326). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 43327). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation	RCV003389445	SCV003927095	pathogenic	Usher syndrome	2022-12-31	criteria provided, single submitter	research
Counsyl	RCV000667735	SCV000792234	pathogenic	Autosomal recessive nonsyndromic hearing loss 2	2017-06-13	no assertion criteria provided	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003080	SCV001161139	likely pathogenic	Usher syndrome type 1	2019-06-23	no assertion criteria provided	research
Natera, Inc.	RCV001835646	SCV002093128	pathogenic	Usher syndrome type 1B	2020-05-27	no assertion criteria provided	clinical testing