Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000642722 | SCV000764409 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-11-15 | criteria provided, single submitter | clinical testing | This sequence change affects codon 16566 of the TTN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TTN protein. This variant is present in population databases (rs778112130, ExAC 0.01%). This variant has not been reported in the literature in individuals with TTN-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant identified in the TTN gene is located in the A band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. 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 | RCV002424455 | SCV002728838 | likely benign | Cardiovascular phenotype | 2019-10-04 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |