ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.44323G>A (p.Val14775Met)

gnomAD frequency: 0.00010  dbSNP: rs540115992
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000694203 SCV000822636 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-09-26 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 14775 of the TTN protein (p.Val14775Met). The valine residue is conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs540115992, ExAC 0.08%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with TTN-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756842 SCV000884783 uncertain significance not provided 2018-03-15 criteria provided, single submitter clinical testing The TTN c.36619G>A; p.Val12207Met variant is rare in the general population (<1% 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. While the clinical significance of such variants is considered uncertain, evidence suggests that vast majority of missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Given the available evidence, the clinical significance of the p.Val12207Met variant cannot be determined with certainty.
Athena Diagnostics Inc RCV000756842 SCV001474991 likely benign not provided 2019-09-26 criteria provided, single submitter clinical testing
GeneDx RCV000756842 SCV001813712 likely benign not provided 2019-06-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV002397410 SCV002712289 uncertain significance Cardiovascular phenotype 2020-01-02 criteria provided, single submitter clinical testing The p.V5710M variant (also known as c.17128G>A), located in coding exon 67 of the TTN gene, results from a G to A substitution at nucleotide position 17128. The valine at codon 5710 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly 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.
Revvity Omics, Revvity RCV000756842 SCV003818463 uncertain significance not provided 2020-11-05 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000756842 SCV004225873 uncertain significance not provided 2023-01-12 criteria provided, single submitter clinical testing

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