ClinVar Miner

Submissions for variant NM_003476.5(CSRP3):c.369T>A (p.Cys123Ter)

gnomAD frequency: 0.00001  dbSNP: rs1216811263
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001037848 SCV001201280 pathogenic Hypertrophic cardiomyopathy 12; Dilated cardiomyopathy 1M 2023-08-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 836666). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 30012424). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Cys123*) in the CSRP3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CSRP3 are known to be pathogenic (PMID: 12642359, 14567970, 16352453, 20087448, 34558151).
AiLife Diagnostics, AiLife Diagnostics RCV001784576 SCV002503182 uncertain significance not provided 2021-12-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002354984 SCV002624107 pathogenic Cardiovascular phenotype 2023-09-19 criteria provided, single submitter clinical testing The p.C123* variant (also known as c.369T>A), located in coding exon 3 of the CSRP3 gene, results from a T to A substitution at nucleotide position 369. This changes the amino acid from a cysteine to a stop codon within coding exon 3. This variant has been reported in a homozygous hypertrophic cardiomyopathy case with a known family history of consanguinity (Janin A et al. Gene, 2018 Nov;676:110-116). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation; however, in the heterozygous state, this variant may present with reduced penetrance and expressivity.

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