ClinVar Miner

Submissions for variant NM_000338.3(SLC12A1):c.2255C>T (p.Ala752Val) (rs137893258)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000315297 SCV000391487 uncertain significance Bartter syndrome, type 1, antenatal 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735359 SCV000854513 uncertain significance Failure to thrive; Sensory neuropathy; Generalized hypotonia; Broad-based gait; Sensory ataxic neuropathy; Decreased body weight; Impaired distal proprioception; Sensory ataxia criteria provided, single submitter clinical testing
Invitae RCV001241458 SCV001414476 uncertain significance not provided 2019-09-06 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 752 of the SLC12A1 protein (p.Ala752Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs137893258, ExAC 0.2%). This variant has not been reported in the literature in individuals with SLC12A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 316268). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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