ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1326C>G (p.Asn442Lys)

gnomAD frequency: 0.00001  dbSNP: rs775232139
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002019805 SCV002284447 likely pathogenic not provided 2022-02-27 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 442 of the SLC12A3 protein (p.Asn442Lys). This variant is present in population databases (rs775232139, gnomAD 0.01%). This missense change has been observed in individual(s) with Gitelman syndrome (PMID: 18581727, 33024574). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 not expected to disrupt SLC12A3 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005017044 SCV005639244 likely pathogenic Familial hypokalemia-hypomagnesemia 2024-03-27 criteria provided, single submitter clinical testing

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