Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CHEO Genetics Diagnostic Laboratory, |
RCV000768828 | SCV000900201 | uncertain significance | Cardiomyopathy | 2016-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002397535 | SCV002674847 | uncertain significance | Cardiovascular phenotype | 2019-05-02 | criteria provided, single submitter | clinical testing | The p.E25707G variant (also known as c.77120A>G), located in coding exon 185 of the TTN gene, results from an A to G substitution at nucleotide position 77120. The glutamic acid at codon 25707 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly 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. |
Invitae | RCV002536605 | SCV003258128 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 34772 of the TTN protein (p.Glu34772Gly). This variant is present in population databases (rs766674127, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of TTN-related conditions (PMID: 32039858). ClinVar contains an entry for this variant (Variation ID: 626395). 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). 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. |