Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003388535 | SCV004100224 | uncertain significance | not specified | 2023-09-27 | criteria provided, single submitter | clinical testing | Variant summary: ETFDH c.245C>T (p.Ser82Phe) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251430 control chromosomes. c.245C>T has been reported in the literature in a homozygous state in an individual affected with adolescent onset Glutaric Aciduria and in a compound heterozygous state in another individual with childhood onset Glutaric Aciduria (e.g. Behin_2016, Goodman_2002). These data indicate that the variant may be associated with disease. To our knowledge, no e(e.g. Behin_2016, Goodman_2002). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27038534, 12359134). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Prevention |
RCV003420682 | SCV004116156 | uncertain significance | ETFDH-related disorder | 2023-08-03 | criteria provided, single submitter | clinical testing | The ETFDH c.245C>T variant is predicted to result in the amino acid substitution p.Ser82Phe. This variant has been reported in the homozygous state or along with a second variant in two individuals with multiple acyl-CoA dehydrogenase deficiency (Goodman et al 2002. PubMed ID: 12359134; Béhin A et al 2016. PubMed ID: 27038534). This variant is reported in 0.0065% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-159603416-C-T). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV003475572 | SCV004194803 | likely pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2024-01-15 | criteria provided, single submitter | clinical testing |