ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.106795G>C (p.Ala35599Pro)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV002293028 SCV002585829 likely benign not provided 2022-09-01 criteria provided, single submitter clinical testing TTN: PM2:Supporting, BP1, BP4
Ambry Genetics RCV002416561 SCV002676467 uncertain significance Cardiovascular phenotype 2019-12-04 criteria provided, single submitter clinical testing The p.A26534P variant (also known as c.79600G>C), located in coding exon 187 of the TTN gene, results from a G to C substitution at nucleotide position 79600. The alanine at codon 26534 is replaced by proline, 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.
Mayo Clinic Laboratories, Mayo Clinic RCV002293028 SCV004225011 uncertain significance not provided 2023-02-21 criteria provided, single submitter clinical testing BP4
Labcorp Genetics (formerly Invitae), Labcorp RCV005213651 SCV005855723 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2025-01-11 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 35599 of the TTN protein (p.Ala35599Pro). This variant is present in population databases (rs754744644, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1711512). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is located in the M band of TTN (PMID: 25589632). Non-truncating variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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