Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000040866 | SCV000064557 | uncertain significance | not specified | 2013-06-11 | criteria provided, single submitter | clinical testing | The Arg30180His variant in TTN has been identified by our laboratory in 2 indivi duals with DCM (LMM unpublished data) and was not identified in large population studies. Computational analyses (biochemical amino acid properties, conservatio n, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the c linical significance of this variant. |
| Gene |
RCV000730013 | SCV000577378 | uncertain significance | not provided | 2017-03-31 | criteria provided, single submitter | clinical testing | The R30180H variant has been previously reported as a variant of uncertain significance in an individual with dilated cardiomyopathy who harbored variants in additional genes associated with this phenotype (Pugh et al., 2014). The R30180H variant is observed in 4/66704 (0.01%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, the majority of disease associated pathogenic variants in the TTN gene are loss of function and result from truncating variants. However, this substitution occurs at a position that is conserved across species, and is located in the A-band of the titin protein, where the majority of pathogenic truncating variants have been reported. In silico analysis predicts this variant is probably damaging to the protein structure/function. |
| Eurofins Ntd Llc |
RCV000730013 | SCV000857720 | uncertain significance | not provided | 2017-11-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002362660 | SCV002666869 | likely benign | Cardiovascular phenotype | 2020-03-18 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Fulgent Genetics, |
RCV002504917 | SCV002799595 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 | 2022-02-10 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000730013 | SCV003822931 | uncertain significance | not provided | 2019-05-10 | criteria provided, single submitter | clinical testing |