ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.3170T>C (p.Val1057Ala)

gnomAD frequency: 0.00019  dbSNP: rs145940356
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000993421 SCV000237724 likely benign not provided 2021-01-04 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 31983221)
Ambry Genetics RCV000619806 SCV000736878 uncertain significance Cardiovascular phenotype 2019-04-19 criteria provided, single submitter clinical testing The p.V1011A variant (also known as c.3032T>C), located in coding exon 18 of the TTN gene, results from a T to C substitution at nucleotide position 3032. The valine at codon 1011 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Athena Diagnostics RCV000993421 SCV001146368 uncertain significance not provided 2018-11-12 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000993421 SCV002049994 uncertain significance not provided 2022-02-08 criteria provided, single submitter clinical testing The TTN c.3170T>C; p.Val1057Ala variant (rs145940356; ClinVar Variation ID: 202962) is rare in the general population (<0.2% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Val1057Ala variant cannot be determined with certainty.
Revvity Omics, Revvity RCV000993421 SCV003818421 uncertain significance not provided 2021-12-10 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV005404362 SCV006067423 likely benign not specified 2025-04-09 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004734821 SCV005364281 uncertain significance TTN-related disorder 2024-08-10 no assertion criteria provided clinical testing The TTN c.3170T>C variant is predicted to result in the amino acid substitution p.Val1057Ala. This variant has been reported in an individual with dilated cardiomyopathy (Table S3, Mazzarotto et al. 2020. PubMed ID: 31983221). This variant is reported in 0.048% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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