Submissions for variant NM_006888.6(CALM1):c.293A>T (p.Asn98Ile)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005221612	SCV005863417	uncertain significance	Catecholaminergic polymorphic ventricular tachycardia 4; Long QT syndrome 14	2024-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 98 of the CALM1 protein (p.Asn98Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CALM1-related conditions. 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. This variant disrupts the p.Asn98 amino acid residue in CALM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23040497, 24563457, 24816216, 25557436, 26309258). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.