Submissions for variant NM_206933.4(USH2A):c.1039G>C (p.Asp347His)

dbSNP: rs772317024

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001346114	SCV001540289	pathogenic	not provided	2022-09-13	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 1042200). This missense change has been observed in individual(s) with clinical features of Usher syndrome (PMID: 26927203; Invitae). This variant is present in population databases (rs772317024, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 347 of the USH2A protein (p.Asp347His). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp347 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25558175, 33576794). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
CeGaT Center for Human Genetics Tuebingen	RCV001346114	SCV002562983	uncertain significance	not provided	2022-06-01	criteria provided, single submitter	clinical testing	USH2A: PM2, PM3:Supporting, PM5:Supporting, PP4