Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000040935 | SCV000064626 | uncertain significance | not specified | 2012-08-21 | criteria provided, single submitter | clinical testing | The Tyr32163Cys variant in TTN has not been reported in the literature nor previ ously identified in our laboratory. Computational analyses (biochemical amino ac id properties, conservation, PolyPhen2, and SIFT) suggest that the variant may i mpact the protein, though this information is not predictive enough to determine pathogenicity. Additional studies are needed to fully assess the clinical signi ficance of this variant. |
| Invitae | RCV002514156 | SCV003478189 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-07-28 | criteria provided, single submitter | clinical testing | This variant is located in the M band of TTN (PMID: 25589632). Variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 47666). This variant has not been reported in the literature in individuals affected with TTN-related conditions. This variant is present in population databases (rs397517789, gnomAD 0.04%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 34731 of the TTN protein (p.Tyr34731Cys). 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. |