Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV002052401 | SCV002319164 | likely pathogenic | not provided | 2022-03-21 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002300647 | SCV002598575 | likely pathogenic | Mitochondrial trifunctional protein deficiency | 2022-09-22 | criteria provided, single submitter | clinical testing | Variant summary: HADHB c.583C>T (p.Arg195X) 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 in ClinVar and is associated with Mitochondrial Trifunctional Protein Deficiency in HGMD. The variant allele was found at a frequency of 8e-06 in 251486 control chromosomes (gnomAD). To our knowledge, no occurrence of c.583C>T in individuals affected with Mitochondrial Trifunctional Protein Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV002300647 | SCV004199808 | likely pathogenic | Mitochondrial trifunctional protein deficiency | 2023-01-15 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002300647 | SCV004518064 | pathogenic | Mitochondrial trifunctional protein deficiency | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg195*) in the HADHB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HADHB are known to be pathogenic (PMID: 9259266, 12754706). This variant is present in population databases (rs552292698, gnomAD 0.003%). 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: 1526383). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |