Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000376635 | SCV000429557 | uncertain significance | Mitochondrial trifunctional protein deficiency | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV000376635 | SCV001418686 | uncertain significance | Mitochondrial trifunctional protein deficiency | 2022-06-09 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 91 of the HADHB protein (p.Thr91Ile). This variant is present in population databases (rs145712438, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with HADHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 335404). 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"). 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. |
| Mayo Clinic Laboratories, |
RCV001507553 | SCV001713161 | uncertain significance | not provided | 2020-09-21 | criteria provided, single submitter | clinical testing | |
| Breakthrough Genomics, |
RCV001507553 | SCV005187987 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Prevention |
RCV004755884 | SCV005352724 | uncertain significance | HADHB-related disorder | 2024-06-24 | no assertion criteria provided | clinical testing | The HADHB c.272C>T variant is predicted to result in the amino acid substitution p.Thr91Ile. This variant was reported in an individual with a myopathy phenotype and elevated CK levels (Supplementary Table S1, Invernizzi et al 2023. PubMed ID: 37510298). This variant is reported in 0.010% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |