ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.20_21del (p.Thr7fs)

dbSNP: rs750710315
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008775 SCV001168565 pathogenic not provided 2024-06-26 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17699451, 21415153, 35628451, 31672324, 20675610)
Labcorp Genetics (formerly Invitae), Labcorp RCV001008775 SCV002247370 pathogenic not provided 2022-05-20 criteria provided, single submitter clinical testing This variant is present in population databases (rs750710315, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Thr7Argfs*22) in the SLC12A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC12A3 are known to be pathogenic (PMID: 20848653, 22009145, 25841442). This premature translational stop signal has been observed in individual(s) with Gitelman syndrome (PMID: 20675610, 21415153, 31672324). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 817609).
Mendelics RCV002249628 SCV002519747 pathogenic Familial hypokalemia-hypomagnesemia 2022-05-04 criteria provided, single submitter clinical testing
Sydney Genome Diagnostics, Children's Hospital Westmead RCV001328167 SCV001449426 likely pathogenic Familial hypokalemia-hypomagnesemia; Bartter syndrome 2018-05-29 no assertion criteria provided clinical testing This patient is heterozygous for the two base deletion (c.20_21del) in exon 1 of SLC12A3 gene. This frameshifting variant is predicted to create a premature stop codon (p.Thr7Argfs*22) and may result in a null allele due to nonsense-mediated mRNA decay. To our knowledge, c.20_21del has not been previously reported to be a disease causing variant and it has not been reported in the ExAC allele frequency database (http://exac.broadinstitute.org). According to ACMG guidelines, this variant is considered to be likely pathogenic.

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