ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1335+1G>A

dbSNP: rs757471117
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001723291 SCV002558339 likely pathogenic not provided 2022-01-28 criteria provided, single submitter clinical testing Observed with a second variant (phase unknown) in a patient with clinical suspicion of Gitelman syndrome in published literature (Glaudemans et al., 2012); Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Different splice changes at this residue (c.1335+1G>T, c.1335+1G>C) have been reported the Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 22009145)
Labcorp Genetics (formerly Invitae), Labcorp RCV001723291 SCV004297741 likely pathogenic not provided 2023-02-26 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 1297510). Disruption of this splice site has been observed in individual(s) with Gitelman syndrome (PMID: 22009145). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change affects a donor splice site in intron 10 of the SLC12A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC12A3 are known to be pathogenic (PMID: 20848653, 22009145, 25841442).
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001723291 SCV001958886 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001723291 SCV001967564 likely pathogenic not provided no assertion criteria provided clinical testing

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