Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001346725 | SCV001540950 | uncertain significance | Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A | 2022-03-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 123 of the MOCS1 protein (p.Arg123Trp). This variant is present in population databases (rs779592342, gnomAD 0.007%). This missense change has been observed in individual(s) with molybdenum cofactor deficiency (PMID: 12754701). ClinVar contains an entry for this variant (Variation ID: 1042726). 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001346725 | SCV005726768 | pathogenic | Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A | 2024-11-11 | criteria provided, single submitter | clinical testing | Variant summary: MOCS1 c.367C>T (p.Arg123Trp) results in a non-conservative amino acid change located in the Radical SAM core domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 249838 control chromosomes (gnomAD). c.367C>T has been reported in the literature in multiple individuals affected with Sulfite Oxidase Deficiency Due To Molybdenum Cofactor Deficiency Type A (e.g. Reiss_2003, Spiegel_2022). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 12754701, 35192225). ClinVar contains an entry for this variant (Variation ID: 1042726). Based on the evidence outlined above, the variant was classified as pathogenic. |