Submissions for variant NM_000441.2(SLC26A4):c.2027T>A (p.Leu676Gln)

dbSNP: rs111033318

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169448	SCV000220869	likely pathogenic	Pendred syndrome	2014-11-11	criteria provided, single submitter	literature only
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV001170043	SCV001251821	likely pathogenic	not provided	2020-05-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001170043	SCV001385304	pathogenic	not provided	2023-12-01	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 676 of the SLC26A4 protein (p.Leu676Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SLC26A4-related conditions (PMID: 12676893, 14715652, 21961810). 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: 43533). 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%. Experimental studies have shown that this missense change affects SLC26A4 function (PMID: 14715652, 18310264). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000770856	SCV002026961	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000169448	SCV002026963	pathogenic	Pendred syndrome	2021-09-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000770856	SCV004201886	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2024-02-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001170043	SCV005078890	pathogenic	not provided	2024-02-09	criteria provided, single submitter	clinical testing	Published functional studies demonstrate defective transported activity and intracellular retention (PMID: 14715652, 18310264); Not observed at 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: 21154317, 36107570, 35853923, 34943614, 14715652, 18310264, 12676893, 21961810, 25015771, 32868181, 32645618, 33724713, 34170635, 35982127, 36833263, 25266519, 34426522, 32877901, 31541171, 30896630, 30275481)
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004795955	SCV005418683	pathogenic	Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome		criteria provided, single submitter	clinical testing	PM2_Supporting+PS3_Supporting+PM3_VeryStrong
Fulgent Genetics, Fulgent Genetics	RCV004795955	SCV005673657	pathogenic	Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome	2024-05-21	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036468	SCV000060123	pathogenic	Rare genetic deafness	2007-06-19	no assertion criteria provided	clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV000770856	SCV000902360	likely pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2019-02-26	no assertion criteria provided	case-control
Natera, Inc.	RCV000169448	SCV001459937	pathogenic	Pendred syndrome	2020-09-16	no assertion criteria provided	clinical testing