ClinVar Miner

Submissions for variant NM_003098.3(SNTA1):c.1339C>T (p.Arg447Ter)

gnomAD frequency: 0.00001  dbSNP: rs1187536758
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV000678954 SCV000805169 uncertain significance Long QT syndrome 12 2018-04-30 criteria provided, single submitter clinical testing
Invitae RCV002531398 SCV002932395 uncertain significance Long QT syndrome 2022-03-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg447*) in the SNTA1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SNTA1 cause disease. This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 560703). This premature translational stop signal has been observed in individual(s) with clinical features of long QT syndrome (PMID: 31737537).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003317336 SCV004020912 uncertain significance not specified 2023-06-19 criteria provided, single submitter clinical testing Variant summary: SNTA1 c.1339C>T (p.Arg447X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, however the molecular mechanism of disease attributed to SNTA1 is gain-of-function. The variant was absent in 251410 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1339C>T has been reported in the literature as a VUS in at least one individual with suspected arrhythmia without strong evidence for causality (e.g., Marschall_2019). This report does not provide unequivocal conclusions about association of the variant with Long QT Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 31737537). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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