Submissions for variant NM_000441.2(SLC26A4):c.1079C>T (p.Ala360Val)

gnomAD frequency: 0.00001  dbSNP: rs786204474

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169123	SCV000220333	likely pathogenic	Pendred syndrome	2014-05-21	criteria provided, single submitter	literature only
Invitae	RCV000808026	SCV000948110	pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 360 of the SLC26A4 protein (p.Ala360Val). This variant is present in population databases (rs786204474, gnomAD 0.06%). This missense change has been observed in individual(s) with hearing loss (PMID: 17697873, 21961810, 23838540, 26252218, 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: 188793). 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 SLC26A4 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000808026	SCV001786324	pathogenic	not provided	2023-07-14	criteria provided, single submitter	clinical testing	Published functional studies demonstrate this variant impairs SLC26A4 protein localization and function (Yuan et al., 2012); Not observed at a significant frequency in large population cohorts (gnomAD); 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: 30842343, 23185506, 26969326, 23838540, 21154317, 17697873, 21961810, 26252218, 27771369, 30275481, 31541171, 24612839, 24341454, 23151025, 33199029, 32447495, 36362242, 35982127, 34416374, 33907123, 32658404)
Genome-Nilou Lab	RCV000770860	SCV002026798	likely pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000169123	SCV002026810	likely pathogenic	Pendred syndrome	2021-09-05	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000808026	SCV003814590	likely pathogenic	not provided	2022-11-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000770860	SCV004201863	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2023-09-18	criteria provided, single submitter	clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV000770860	SCV000902367	likely pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2019-02-26	no assertion criteria provided	case-control
Natera, Inc.	RCV000169123	SCV001455808	pathogenic	Pendred syndrome	2020-09-16	no assertion criteria provided	clinical testing