Submissions for variant NM_000441.2(SLC26A4):c.2326C>T (p.Arg776Cys)

gnomAD frequency: 0.00183  dbSNP: rs111033255

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036483	SCV000060138	likely benign	not specified	2015-07-02	criteria provided, single submitter	clinical testing	p.Arg776Cys in exon 21 of SLC26A4: This variant has been reported in six proband s with non-syndromic hearing loss with/without EVA (Pryor 2005, Choi 2009, Hutch in 2005, Pourova 2010). However, haplotype analysis in one of the reported famil ies showed inconsistent segregation of the SLC26A4 gene in an affected sibling, suggesting that SLC26A4 mutations were not the primary cause of hearing loss in that family. This variant has been identified in 0.5% (33/6614) of Finnish chro mosomes and in 0.3% (192/66740) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs111033255). In addit ion, this variant has now been identified in our laboratory in 2 patients with a nother genetic cause of their hearing loss. In addition, two independent functio nal studies show that the variant allele had a similar function to wildtype (Pfa rr 2006, Choi 2009). In summary, the current data suggest that this variant is l ikely benign.
GeneDx	RCV000036483	SCV000730014	likely benign	not specified	2017-12-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000036483	SCV000854862	likely benign	not specified	2017-08-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757778	SCV000886133	likely benign	not provided	2020-02-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000757778	SCV001023699	likely benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001159992	SCV001321753	uncertain significance	Pendred syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001159993	SCV001321754	uncertain significance	Autosomal recessive nonsyndromic hearing loss 4	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV001159993	SCV002027550	likely benign	Autosomal recessive nonsyndromic hearing loss 4	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001159992	SCV002027562	likely benign	Pendred syndrome	2021-09-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000757778	SCV004699298	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	SLC26A4: BS1
Natera, Inc.	RCV001159992	SCV001463985	uncertain significance	Pendred syndrome	2020-01-02	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000757778	SCV001979672	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000757778	SCV001980643	uncertain significance	not provided		no assertion criteria provided	clinical testing