Submissions for variant NM_000441.2(SLC26A4):c.1975G>C (p.Val659Leu)

gnomAD frequency: 0.00001  dbSNP: rs200455203

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169245	SCV000220524	likely pathogenic	Pendred syndrome	2014-07-17	criteria provided, single submitter	literature only
Division of Hearing and Balance Research, National Hospital Organization Tokyo Medical Center	RCV000515737	SCV000611821	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2017-07-01	criteria provided, single submitter	clinical testing
Invitae	RCV001048975	SCV001213005	pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 659 of the SLC26A4 protein (p.Val659Leu). This variant is present in population databases (rs200455203, gnomAD 0.02%). This missense change has been observed in individual(s) with enlarged vestibular aqueduct (PMID: 17443271, 21366435, 21961810, 22289209, 23385134, 25266519, 25372295, 26100058). 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: 188889). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC26A4 protein function. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000515737	SCV002026959	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000169245	SCV002026960	pathogenic	Pendred syndrome	2021-09-05	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001048975	SCV003821119	pathogenic	not provided	2022-06-10	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000515737	SCV004201868	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2023-09-11	criteria provided, single submitter	clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV000515737	SCV000902378	likely pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2019-02-26	no assertion criteria provided	case-control
National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center	RCV000515737	SCV000994902	affects	Autosomal recessive nonsyndromic hearing loss 4	2019-08-20	no assertion criteria provided	clinical testing	in vitro experiment