Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519729 | SCV000617537 | uncertain significance | not provided | 2022-12-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies suggest that this variant negatively impacts protein folding (PMID: 23297410); however, the actual effect of this sequence change is unknown; Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; The p.(T2896I) variant has been reported to segregate with ARVC in multiple members of one family (PMID: 21810661); This variant is associated with the following publications: (PMID: 27683155, 25157032, 24980681, 33530662, 21810661, 31402444, 31028357, 33831308, 32927679, 32466575, 33429969, 23297410) |
Invitae | RCV000527160 | SCV000643823 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-04-25 | criteria provided, single submitter | clinical testing | 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. This variant is located in the I band of TTN (PMID: 25589632). Variants in this region may be clinically relevant, but have not been definitively shown to cause cardiomyopathy or neuromuscular disease (PMID: 27493940, 32778822). Experimental studies have shown that this missense change affects TTN function (PMID: 21810661, 23297410). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 449405). This missense change has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) (PMID: 21810661). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2896 of the TTN protein (p.Thr2896Ile). |