Submissions for variant NM_000260.4(MYO7A):c.3508G>A (p.Glu1170Lys)

gnomAD frequency: 0.00004  dbSNP: rs111033214

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000664470	SCV000788432	pathogenic	Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2017-02-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763278	SCV000893922	pathogenic	Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2022-02-17	criteria provided, single submitter	clinical testing
Mendelics	RCV000988609	SCV001138388	pathogenic	Autosomal recessive nonsyndromic hearing loss 2	2019-05-28	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001075104	SCV001240715	pathogenic	Retinal dystrophy	2018-08-02	criteria provided, single submitter	clinical testing
Invitae	RCV001385688	SCV001585637	pathogenic	not provided	2023-12-14	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1170 of the MYO7A protein (p.Glu1170Lys). This variant is present in population databases (rs111033214, gnomAD 0.01%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 10425080, 15043528, 21436283). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 43208). 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.
GeneDx	RCV001385688	SCV001824526	pathogenic	not provided	2022-01-24	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23451239, 16470552, 12112664, 16679490, 21311020, 27460420, 21436283, 18181211, 31479088, 16652077, 10447383, 33671976, 26791358, 30081015, 30303587, 10425080, 31589614, 33576163, 15043528)
PreventionGenetics, part of Exact Sciences	RCV003952413	SCV004772940	pathogenic	MYO7A-related condition	2023-11-28	criteria provided, single submitter	clinical testing	The MYO7A c.3508G>A variant is predicted to result in the amino acid substitution p.Glu1170Lys. This variant has been reported as causative for Usher syndrome (Cuevas et al. 1999. PubMed ID: 10425080; Nájera et al 2002. PubMed ID: 12112664; Table S1, Bonnet et al. 2016. PubMed ID: 27460420, Roux et al. 2011. PubMed ID: 21436283). This variant is reported in 0.010% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant is interpreted as pathogenic.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036112	SCV000059764	pathogenic	Rare genetic deafness	2006-10-28	no assertion criteria provided	clinical testing
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291476	SCV001479980	likely pathogenic	Hearing loss, autosomal recessive		no assertion criteria provided	research
Natera, Inc.	RCV001826545	SCV002086671	pathogenic	Usher syndrome type 1B	2020-07-08	no assertion criteria provided	clinical testing