ClinVar Miner

Submissions for variant NM_001232.4(CASQ2):c.481A>G (p.Ile161Val)

gnomAD frequency: 0.00076  dbSNP: rs146333579
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037143 SCV000060800 uncertain significance not specified 2012-02-14 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ile161Val varia nt (CASQ2) has been identified in 3/7020 European American chromosomes from a br oad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS; dbSNP rs146333579). Computational analyses (biochemical amino acid prope rties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Ile161Val variant may not impact the protein, though this information is not predictive en ough to rule out pathogenicity. Additional information is needed to fully assess the clinical significance of this variant.
Ambry Genetics RCV000244068 SCV000318909 likely benign Cardiovascular phenotype 2020-08-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV003103723 SCV000548686 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 161 of the CASQ2 protein (p.Ile161Val). This variant is present in population databases (rs146333579, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CASQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 44167). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CASQ2 protein function. 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 RCV001719739 SCV000565915 uncertain significance not provided 2021-01-13 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28404607)

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