ClinVar Miner

Submissions for variant NM_001743.6(CALM2):c.104C>T (p.Thr35Ile)

gnomAD frequency: 0.00001  dbSNP: rs757523692
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004577350 SCV001419347 uncertain significance Long QT syndrome 1 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 35 of the CALM2 protein (p.Thr35Ile). This variant is present in population databases (rs757523692, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CALM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 970445). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
GeneDx RCV002272427 SCV002558142 uncertain significance not provided 2022-07-28 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD)
Ambry Genetics RCV002402782 SCV002705424 uncertain significance Cardiovascular phenotype 2023-05-30 criteria provided, single submitter clinical testing The p.T35I variant (also known as c.104C>T), located in coding exon 3 of the CALM2 gene, results from a C to T substitution at nucleotide position 104. The threonine at codon 35 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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