Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000155590 | SCV000205298 | likely benign | not specified | 2013-03-27 | criteria provided, single submitter | clinical testing | The Lys33318Arg variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. This variant has also not been identified in large and broad European American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS), though it may be c ommon in other populations. The variant amino acid (arginine, Arg) is present in other species, including many mammals. It is therefore highly unlikely that th is variant causes disease although a modifying effect cannot be ruled out. |
Gene |
RCV003441758 | SCV000722511 | uncertain significance | not provided | 2023-10-31 | criteria provided, single submitter | clinical testing | Located in the M-line region of TTN in which the majority of loss of function variants have been associated with autosomal recessive titinopathies (PMID: 17444505); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30453078, 17444505) |
Invitae | RCV001850129 | SCV002150774 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 35886 of the TTN protein (p.Lys35886Arg). This variant is present in population databases (rs727504465, gnomAD 0.005%). This missense change has been observed in individual(s) with arrhythmogenic cardiomyopathy (PMID: 30453078). ClinVar contains an entry for this variant (Variation ID: 178818). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |