ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.7618C>T (p.Arg2540Cys)

gnomAD frequency: 0.00011  dbSNP: rs368574470
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537759 SCV000643678 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-03-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619486 SCV000736709 uncertain significance Cardiovascular phenotype 2019-11-26 criteria provided, single submitter clinical testing The p.R2494C variant (also known as c.7480C>T), located in coding exon 31 of the TTN gene, results from a C to T substitution at nucleotide position 7480. The arginine at codon 2494 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly 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 Inc RCV000714095 SCV000844762 uncertain significance not provided 2018-07-24 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000714095 SCV000855290 uncertain significance not provided 2018-02-06 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170103 SCV001332642 likely benign Cardiomyopathy 2023-01-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193720 SCV001362769 uncertain significance not specified 2019-10-07 criteria provided, single submitter clinical testing Variant summary: TTN c.7618C>T (p.Arg2540Cys) results in a non-conservative amino acid change located in the I-band region of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 249808 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Cardiomyopathy (5.2e-05 vs 0.00063), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.7618C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. In an internal LCA specimen this variant co-occurred with another pathogenic variant (MYH7 c.2539A>G, p.Lys847Glu), providing supporting evidence for a benign role. Four ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002476170 SCV002775094 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 2021-11-17 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000714095 SCV003820329 uncertain significance not provided 2023-11-15 criteria provided, single submitter clinical testing

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