Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001233682 | SCV001406287 | uncertain significance | Pyruvate dehydrogenase E1-alpha deficiency | 2019-10-29 | 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. This variant disrupts the p.Ile177 amino acid residue in PDHA1. Other variant(s) that disrupt this residue have been observed in individuals with PDHA1-related conditions (PMID: 28918066), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PDHA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 177 of the PDHA1 protein (p.Ile177Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. |