Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000473391 | SCV000542327 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 34709 of the TTN protein (p.Arg34709Cys). This variant is present in population databases (rs530959653, gnomAD 0.008%). 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: 404669). 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. |
Ambry Genetics | RCV000617739 | SCV000737289 | uncertain significance | Cardiovascular phenotype | 2017-07-12 | criteria provided, single submitter | clinical testing | The p.R25644C variant (also known as c.76930C>T), located in coding exon 185 of the TTN gene, results from a C to T substitution at nucleotide position 76930. The arginine at codon 25644 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and to have low/neutral functional impact by PolyPhen and Mutation Assessor in silico analyses, respectively (Reva B et al. Genome Biol. 2007;8(11):R232). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV001578025 | SCV001805544 | likely benign | not provided | 2021-04-07 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge |
Athena Diagnostics | RCV001578025 | SCV002770636 | uncertain significance | not provided | 2022-09-02 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001578025 | SCV003825492 | uncertain significance | not provided | 2021-07-21 | criteria provided, single submitter | clinical testing |