Submissions for variant NM_153676.4(USH1C):c.1136G>A (p.Gly379Asp)

gnomAD frequency: 0.00008  dbSNP: rs202174251

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041250	SCV000064941	uncertain significance	not specified	2020-03-04	criteria provided, single submitter	clinical testing	The p.Gly379Asp variant in USH1C has been reported in one family with Usher syndrome; however, a second USH1C variant was not identified on the other allele (Aparisi 2010). It has also been identified by our laboratory in 1 proband with hearing loss who had an alternate genetic etiology identified. This variant is present in 0.02% (22/129188) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org), and it has been reported in ClinVar (Variation ID 47975). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3.
Invitae	RCV001244821	SCV001418065	uncertain significance	not provided	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 379 of the USH1C protein (p.Gly379Asp). This variant is present in population databases (rs202174251, gnomAD 0.02%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 21203349). ClinVar contains an entry for this variant (Variation ID: 47975). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Natera, Inc.	RCV001273249	SCV001456079	uncertain significance	Usher syndrome type 1C	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001244821	SCV001922943	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001244821	SCV001970229	uncertain significance	not provided		no assertion criteria provided	clinical testing