Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155836 | SCV003845020 | likely pathogenic | Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 | 2023-02-20 | criteria provided, single submitter | clinical testing | Variant summary: TSFM c.614delA (p.Asp205ValfsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251016 control chromosomes. To our knowledge, no occurrence of c.614delA in individuals affected with Combined Oxidative Phosphorylation Deficiency 3 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV003669360 | SCV004397377 | pathogenic | not provided | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp205Valfs*5) in the TSFM gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 142 amino acid(s) of the TSFM protein. This variant is present in population databases (rs779144962, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TSFM-related conditions. ClinVar contains an entry for this variant (Variation ID: 2445917). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the TSFM protein in which other variant(s) (p.Arg333Trp) have been determined to be pathogenic (PMID: 17033963, 21741925, 22277967). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV003155836 | SCV005629974 | likely pathogenic | Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 | 2024-03-10 | criteria provided, single submitter | clinical testing |