Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188052 | SCV000241655 | uncertain significance | not provided | 2014-01-08 | criteria provided, single submitter | clinical testing | p.Ser30Phe (TCC>TTC): c.89 C>T in exon 2 of the LIAS gene (NM_006859.2). The Ser30Phe missense change in the LIAS gene has not been published as a mutation, nor has it been reported as a benign polymorphism. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of a polar Serine residue with a non-polar Phenylalanine residue at a position that is not highly conserved across species. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Ser30Phe is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Invitae | RCV001303796 | SCV001493054 | uncertain significance | Lipoic acid synthetase deficiency | 2022-02-08 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 30 of the LIAS protein (p.Ser30Phe). This variant is present in population databases (rs796052701, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with LIAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 206043). 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 phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |