Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000647107 | SCV000768894 | uncertain significance | Dilated cardiomyopathy 1Z; Hypertrophic cardiomyopathy 13 | 2017-12-21 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TNNC1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 53 of the TNNC1 protein (p.Thr53Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. |
Laboratory for Molecular Medicine, |
RCV000825474 | SCV000966776 | uncertain significance | not specified | 2018-04-04 | criteria provided, single submitter | clinical testing | The p.Thr53Ala variant in TNNC1 has not been previously reported in individuals with cardiomyopathy and was absent from large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p .Thr53Ala variant is uncertain. ACMG/AMP Criteria applied: PM2 |
Genome Diagnostics Laboratory, |
RCV001579329 | SCV001806824 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV001579329 | SCV001923760 | uncertain significance | not provided | no assertion criteria provided | clinical testing |