Submissions for variant NM_000441.2(SLC26A4):c.1371C>A (p.Asn457Lys)

dbSNP: rs1554359670

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000664842	SCV000788860	likely pathogenic	Pendred syndrome	2016-12-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001855431	SCV002241394	pathogenic	not provided	2023-10-06	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 457 of the SLC26A4 protein (p.Asn457Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Pendred syndrome and deafness (PMID: 12676893, 20597900). 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: 550172). 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. Experimental studies have shown that this missense change affects SLC26A4 function (PMID: 31599023). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV001004642	SCV004201845	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2023-11-19	criteria provided, single submitter	clinical testing
National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center	RCV001004642	SCV000994892	affects	Autosomal recessive nonsyndromic hearing loss 4	2019-08-20	no assertion criteria provided	literature only	in vitro experiment