ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.94747C>T (p.Arg31583Cys)

gnomAD frequency: 0.00001  dbSNP: rs994448356
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002369231 SCV002661588 uncertain significance Cardiovascular phenotype 2020-02-21 criteria provided, single submitter clinical testing The p.R22518C variant (also known as c.67552C>T), located in coding exon 168 of the TTN gene, results from a C to T substitution at nucleotide position 67552. The arginine at codon 22518 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003322916 SCV004028179 uncertain significance not provided 2023-02-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; Has not been previously published as pathogenic or benign to our knowledge
Clinical Genomics Laboratory, Washington University in St. Louis RCV004559413 SCV005047074 uncertain significance Dilated cardiomyopathy 1G 2024-04-04 criteria provided, single submitter clinical testing A TTN c.94747C>T (p.Arg31583Cys) variant was identified. This variant, to our knowledge, has not been reported in the medical literature in individuals with TTN-related conditions. This variant has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters (ClinVar Variation ID: 1755250). The TTN c.94747C>T (p.Arg31583Cys) variant is absent from the general population (gnomAD v2.1.1). Computational predictors are uncertain as to the impact of this variant on TTN function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004700738 SCV005202195 uncertain significance not specified 2024-07-01 criteria provided, single submitter clinical testing Variant summary: TTN c.87043C>T (p.Arg29015Cys) results in a non-conservative amino acid change located in the A-band of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248338 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.87043C>T 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: 1755250). Based on the evidence outlined above, the variant was classified as uncertain significance.

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