Submissions for variant NM_000260.4(MYO7A):c.2387G>A (p.Arg796Gln)

gnomAD frequency: 0.00008  dbSNP: rs111033224

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036086	SCV000059738	uncertain significance	not specified	2008-03-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000665257	SCV000789348	uncertain significance	Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2017-01-27	criteria provided, single submitter	clinical testing
Invitae	RCV001296514	SCV001485480	uncertain significance	not provided	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 796 of the MYO7A protein (p.Arg796Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 43182). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYO7A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001296514	SCV001997496	uncertain significance	not provided	2019-12-24	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001296514	SCV001954239	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001296514	SCV001975185	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826542	SCV002086615	uncertain significance	Usher syndrome type 1B	2020-10-14	no assertion criteria provided	clinical testing