ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.45369C>G (p.Ile15123Met)

gnomAD frequency: 0.00001  dbSNP: rs1160173197
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618607 SCV000735512 uncertain significance Cardiovascular phenotype 2018-10-26 criteria provided, single submitter clinical testing The p.I6058M variant (also known as c.18174C>G), located in coding exon 73 of the TTN gene, results from a C to G substitution at nucleotide position 18174. The isoleucine at codon 6058 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001280577 SCV001467782 uncertain significance not specified 2020-12-14 criteria provided, single submitter clinical testing Variant summary: TTN c.37665C>G (p.Ile12555Met) results in a conservative amino acid change located in the I-band domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245922 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.37665C>G in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One co-occurrence with another pathogenic variant has been reported internally (TTN c.81493+1G>C), providing supporting evidence for a benign role. One ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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