Submissions for variant NM_003476.5(CSRP3):c.365G>A (p.Arg122Gln)

gnomAD frequency: 0.00004  dbSNP: rs193922667

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029622	SCV000052274	likely pathogenic	Cardiomyopathy	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Likely pathogenic.
Invitae	RCV000653699	SCV000775582	likely pathogenic	Hypertrophic cardiomyopathy 12; Dilated cardiomyopathy 1M	2023-09-12	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 122 of the CSRP3 protein (p.Arg122Gln). This variant is present in population databases (rs193922667, gnomAD 0.004%). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 33012304; Invitae). ClinVar contains an entry for this variant (Variation ID: 35966). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics	RCV002453271	SCV002613477	uncertain significance	Cardiovascular phenotype	2018-06-01	criteria provided, single submitter	clinical testing	The p.R122Q variant (also known as c.365G>A), located in coding exon 3 of the CSRP3 gene, results from a G to A substitution at nucleotide position 365. The arginine at codon 122 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529100	SCV001741973	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001529100	SCV001920494	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529100	SCV001929375	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529100	SCV001955298	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529100	SCV001965509	uncertain significance	not provided		no assertion criteria provided	clinical testing