Submissions for variant NM_001232.4(CASQ2):c.421-14G>A

gnomAD frequency: 0.00159  dbSNP: rs139281637

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037140	SCV000060797	uncertain significance	not specified	2016-07-01	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The c.421-14G>A var iant in CASQ2 has been reported in 6 individuals with different cardiomyopathies (HCM, DCM, LVNC, CPVT), two of whom also carried another variant sufficient to explain disease (Laitinen 2003, LMM data). This variant has been identified in 0 .2% (123/66738) of European chromosomes by the Exome Aggregation Consortium (ExA C, http://exac.broadinstitute.org. dbSNP rs139281637). This variant is located i n the 3' splice region. Computational tools do not suggest an impact to splicing . However, this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the c.421-14G>A variant is uncert ain, these data suggest that it is more likely to be benign.
GeneDx	RCV000037140	SCV000223439	benign	not specified	2014-11-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV000625054	SCV000347683	uncertain significance	Catecholaminergic polymorphic ventricular tachycardia 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625054	SCV000743629	benign	Catecholaminergic polymorphic ventricular tachycardia 2	2014-10-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513469	SCV002425744	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-31	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037140	SCV001920978	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952428	SCV004767871	likely benign	CASQ2-related disorder	2021-05-03	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).