Submissions for variant NM_003476.5(CSRP3):c.299G>A (p.Arg100His)

gnomAD frequency: 0.00097  dbSNP: rs138218523

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000143875	SCV000050856	likely benign	Hypertrophic cardiomyopathy	2018-04-05	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037780	SCV000061442	uncertain significance	not specified	2012-03-06	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Arg100His varia nt (CSRP3) has been reported in 1 individual with HCM (Anderson 2009) and has be en detected in 1 individual with HCM tested by our laboratory who carried a path ogenic HCM variant (LMM unpublished data). This variant has been identified in 0.1% (6/7020) of European American chromosomes from a broad population by the NH LBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs13821852 3). While this frequency suggests that it is more likely benign but it is too lo w to confidently rule out a disease causing role. Additional information is need ed to fully assess its clinical significance.
Blueprint Genetics	RCV000037780	SCV000188744	benign	not specified	2015-01-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000514222	SCV000235770	likely benign	not provided	2020-07-16	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23299917, 24082139, 19035361, 23861362, 30012424)
Invitae	RCV001087554	SCV000253397	benign	Hypertrophic cardiomyopathy 12; Dilated cardiomyopathy 1M	2024-01-29	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514222	SCV000610652	likely benign	not provided	2017-08-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617191	SCV000736682	likely benign	Cardiovascular phenotype	2019-02-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000037780	SCV001157233	likely benign	not specified	2019-04-07	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001107280	SCV001264421	uncertain significance	Hypertrophic cardiomyopathy 12	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170413	SCV001332990	benign	Cardiomyopathy	2018-05-04	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037780	SCV002014940	likely benign	not specified	2021-10-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003934915	SCV004756440	likely benign	CSRP3-related condition	2020-09-05	criteria provided, single submitter	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).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000514222	SCV001743846	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000514222	SCV001918319	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000514222	SCV001956985	likely benign	not provided		no assertion criteria provided	clinical testing