ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1216A>C (p.Asn406His)

gnomAD frequency: 0.00008  dbSNP: rs759532318
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center RCV000490283 SCV000267498 uncertain significance Familial hypokalemia-hypomagnesemia 2016-03-18 criteria provided, single submitter reference population
Labcorp Genetics (formerly Invitae), Labcorp RCV002515599 SCV003441842 pathogenic not provided 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 406 of the SLC12A3 protein (p.Asn406His). This variant is present in population databases (rs759532318, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of Gitelman syndrome (PMID: 14655226, 17511264, 26770037, 30596175, 32528714). 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: 225467). 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 SLC12A3 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

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