Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000687239 | SCV000814796 | uncertain significance | Loeys-Dietz syndrome 2 | 2018-03-25 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces lysine with glutamic acid at codon 356 of the TMPO protein (p.Lys356Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs730880229, ExAC 0.002%). This variant has not been reported in the literature in individuals with TMPO-related disease. ClinVar contains an entry for this variant (Variation ID: 180549). 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. |
Blueprint Genetics | RCV000157528 | SCV000207274 | uncertain significance | Primary familial hypertrophic cardiomyopathy | 2013-11-15 | no assertion criteria provided | clinical testing |