Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001246079 | SCV001419417 | uncertain significance | Pyruvate dehydrogenase E1-beta deficiency | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 343 of the PDHB protein (p.Ile343Met). This variant is present in population databases (rs149830613, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with PDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 970499). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PDHB 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. |
Ambry Genetics | RCV004034851 | SCV005003728 | uncertain significance | Inborn genetic diseases | 2021-09-16 | criteria provided, single submitter | clinical testing | The c.1029A>G (p.I343M) alteration is located in exon 10 (coding exon 10) of the PDHB gene. This alteration results from a A to G substitution at nucleotide position 1029, causing the isoleucine (I) at amino acid position 343 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Gene |
RCV004590278 | SCV005081056 | uncertain significance | not provided | 2024-04-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV001280181 | SCV001467341 | uncertain significance | Pyruvate dehydrogenase complex deficiency | 2020-08-18 | no assertion criteria provided | clinical testing |