ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1648G>A (p.Ala550Thr)

gnomAD frequency: 0.00031  dbSNP: rs563131364
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
European Hospital Georges Pompidou Genetics Department, Assistance Publique - Hôpitaux de Paris AP-HP RCV002245160 SCV002513807 uncertain significance Familial hypokalemia-hypomagnesemia 2022-04-27 criteria provided, single submitter clinical testing ACMG criteria used:PM1 PM2 PP3
GeneDx RCV002463179 SCV002757163 uncertain significance not provided 2022-05-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002245160 SCV002775157 uncertain significance Familial hypokalemia-hypomagnesemia 2022-04-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002463179 SCV003278285 uncertain significance not provided 2022-08-17 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 550 of the SLC12A3 protein (p.Ala550Thr). This variant is present in population databases (rs563131364, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with SLC12A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1684161). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity RCV002245160 SCV003823311 uncertain significance Familial hypokalemia-hypomagnesemia 2019-05-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV004045183 SCV004951080 uncertain significance Inborn genetic diseases 2022-04-25 criteria provided, single submitter clinical testing The c.1648G>A (p.A550T) alteration is located in exon 13 (coding exon 13) of the SLC12A3 gene. This alteration results from a G to A substitution at nucleotide position 1648, causing the alanine (A) at amino acid position 550 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics RCV002463179 SCV005194404 uncertain significance not provided criteria provided, single submitter not provided

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