Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001330534 | SCV001522242 | likely pathogenic | Combined malonic and methylmalonic acidemia | 2020-02-26 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001330534 | SCV003922443 | likely pathogenic | Combined malonic and methylmalonic acidemia | 2023-03-03 | criteria provided, single submitter | clinical testing | Variant summary: ACSF3 c.1536G>A (p.Trp512X) 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 reported in association with Malonic & methylmalonic aciduria in HGMD. The variant was absent in 251470 control chromosomes. To our knowledge, no occurrence of c.1536G>A in individuals affected with Combined Malonic And Methylmalonic Aciduria 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 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV001330534 | SCV004518688 | pathogenic | Combined malonic and methylmalonic acidemia | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp512*) in the ACSF3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACSF3 are known to be pathogenic (PMID: 21841779, 26827111). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ACSF3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1029290). For these reasons, this variant has been classified as Pathogenic. |