ClinVar Miner

Submissions for variant NM_006888.6(CALM1):c.4-3T>C

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002333744 SCV002631264 uncertain significance Cardiovascular phenotype 2018-12-31 criteria provided, single submitter clinical testing The c.4-3T>C intronic variant results from a T to C substitution 3 nucleotides upstream from coding exon 2 in the CALM1 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003775885 SCV004592654 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 4; Long QT syndrome 14 2023-11-24 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the CALM1 gene. It does not directly change the encoded amino acid sequence of the CALM1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs754359981, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CALM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1740325). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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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