Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001232566 | SCV001405128 | uncertain significance | Lipoic acid synthetase deficiency | 2019-08-03 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with LIAS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 199 of the LIAS protein (p.Tyr199His). The tyrosine residue is weakly conserved and there is a moderate physicochemical difference between tyrosine and histidine. 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine 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. |