Submissions for variant NM_003476.5(CSRP3):c.312C>G (p.Thr104=)

gnomAD frequency: 0.01721  dbSNP: rs45582433

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037781	SCV000061443	benign	not specified	2009-09-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000037781	SCV000168049	benign	not specified	2013-04-26	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081877	SCV000262087	benign	Hypertrophic cardiomyopathy 12; Dilated cardiomyopathy 1M	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000243280	SCV000319207	benign	Cardiovascular phenotype	2015-06-26	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Illumina Laboratory Services, Illumina	RCV000269525	SCV000369723	likely benign	Hypertrophic cardiomyopathy 12	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587893	SCV000698206	benign	not provided	2017-06-26	criteria provided, single submitter	clinical testing	Variant summary: The CSRP3 c.312C>G (p.Thr104Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 575/121406 control chromosomes (13 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.051989 (541/10406). This frequency is about 2080 times the estimated maximal expected allele frequency of a pathogenic CSRP3 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769304	SCV000900682	benign	Cardiomyopathy	2015-12-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587893	SCV001472830	benign	not provided	2023-11-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001081877	SCV002807237	benign	Hypertrophic cardiomyopathy 12; Dilated cardiomyopathy 1M	2021-09-20	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000587893	SCV005223664	likely benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000587893	SCV001739613	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037781	SCV001922836	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037781	SCV001951891	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004534802	SCV004744625	benign	CSRP3-related disorder	2019-08-12	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).