ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.97642C>T (p.Arg32548Cys)

gnomAD frequency: 0.00014  dbSNP: rs377599569
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000154884 SCV000204566 uncertain significance not specified 2014-06-26 criteria provided, single submitter clinical testing The Arg29980Cys variant in TTN has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 1/3916 African American chromosom es by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/, dbS NP rs377599569). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Arg29980Cys variant is uncertain.
Eurofins Ntd Llc (ga) RCV000726736 SCV000702582 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing
GeneDx RCV000726736 SCV000728198 likely benign not provided 2019-08-09 criteria provided, single submitter clinical testing
Invitae RCV000643170 SCV000764857 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-10-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002372013 SCV002667941 likely benign Cardiovascular phenotype 2020-03-24 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154884 SCV004029901 uncertain significance not specified 2023-07-24 criteria provided, single submitter clinical testing Variant summary: TTN c.89938C>T (p.Arg29980Cys) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 248476 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (5.2e-05 vs 0.00039), allowing no conclusion about variant significance. c.89938C>T has been reported in the literature in individuals affected with Sudden Unexplained Death (SUD, Campuzano_2015). This report does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 26516846). Four ClinVar submitters have assessed the variant since 2014: two classified the variant as uncertain significance and two as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

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