Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000689296 | SCV000816939 | uncertain significance | Loeys-Dietz syndrome 2 | 2020-03-22 | 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine 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 variant has not been reported in the literature in individuals with TMPO-related disease. This variant is present in population databases (rs750751621, ExAC 0.002%). This sequence change replaces arginine with cysteine at codon 230 of the TMPO protein (p.Arg230Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. |
Ambry Genetics | RCV004026323 | SCV002667743 | uncertain significance | not specified | 2023-10-05 | criteria provided, single submitter | clinical testing | The c.688C>T (p.R230C) alteration is located in exon 4 (coding exon 4) of the TMPO gene. This alteration results from a C to T substitution at nucleotide position 688, causing the arginine (R) at amino acid position 230 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |