Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000155971 | SCV000205683 | uncertain significance | not specified | 2013-08-09 | criteria provided, single submitter | clinical testing | The Arg8121Gln variant in TTN has not been reported in individuals with cardiomy opathy or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Arg8121Gln variant may not impact the protein, though this information is not p redictive enough to rule out pathogenicity. In summary, additional information i s needed to fully assess the clinical significance of the Arg8121Gln variant. |
Invitae | RCV000461125 | SCV000542600 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-09-28 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001558815 | SCV001780836 | likely benign | not provided | 2020-08-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000155971 | SCV002555883 | uncertain significance | not specified | 2022-06-14 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.24362G>A (p.Arg8121Gln) results in a conservative amino acid change located in the I band of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 248748 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (4e-05 vs 0.00039), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.24362G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign and uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Revvity Omics, |
RCV001558815 | SCV003820159 | uncertain significance | not provided | 2020-05-29 | criteria provided, single submitter | clinical testing |