ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.66703G>A (p.Val22235Ile)

gnomAD frequency: 0.00011  dbSNP: rs751354601
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000550774 SCV000643550 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-11-04 criteria provided, single submitter clinical testing
GeneDx RCV000607451 SCV000713918 likely benign not specified 2018-01-05 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.
Eurofins Ntd Llc (ga) RCV000727753 SCV000855131 uncertain significance not provided 2017-10-02 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170579 SCV001333167 likely benign Cardiomyopathy 2017-11-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002377097 SCV002624435 uncertain significance Cardiovascular phenotype 2019-12-05 criteria provided, single submitter clinical testing The p.V13170I variant (also known as c.39508G>A), located in coding exon 143 of the TTN gene, results from a G to A substitution at nucleotide position 39508. The valine at codon 13170 is replaced by isoleucine, 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 RCV000727753 SCV003819796 uncertain significance not provided 2023-07-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000607451 SCV005395202 uncertain significance not specified 2024-09-23 criteria provided, single submitter clinical testing Variant summary: TTN c.58999G>A (p.Val19667Ile) results in a conservative amino acid change located in the A band (cardiodb.org) of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.6e-05 in 1612272 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (9.6e-05 vs 0.00039), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.58999G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 467392). Based on the evidence outlined above, the variant was classified as uncertain significance.

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