Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000613481 | SCV000719637 | likely benign | not specified | 2017-05-16 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000613481 | SCV001623242 | uncertain significance | not specified | 2021-05-10 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.197C>T (p.Thr66Met) results in a non-conservative amino acid change located in the Z-disk region (cardiodb.org) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251316 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (4.4e-05 vs 0.00039), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.197C>T in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
CHEO Genetics Diagnostic Laboratory, |
RCV003486892 | SCV004239848 | likely benign | Cardiomyopathy | 2023-01-26 | criteria provided, single submitter | clinical testing |