ClinVar Miner

Submissions for variant NM_001358530.2(MOCS1):c.217C>T (p.Arg73Trp)

gnomAD frequency: 0.00006  dbSNP: rs104893970
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000006495 SCV001490281 likely pathogenic Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A 2024-01-01 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 73 of the MOCS1 protein (p.Arg73Trp). This variant is present in population databases (rs104893970, gnomAD 0.03%). This missense change has been observed in individuals with molybdenum cofactor deficiency (PMID: 9921896, 20573177, 35192225; Invitae). ClinVar contains an entry for this variant (Variation ID: 6121). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000006495 SCV003928248 pathogenic Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A 2023-04-28 criteria provided, single submitter clinical testing Variant summary: MOCS1 c.217C>T (p.Arg73Trp) results in a non-conservative amino acid change located in the Elp3/MiaA/NifB-like, radical SAM core domain (IPR006638) 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 6.4e-05 in 249500 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MOCS1 causing Sulfite Oxidase Deficiency Due To Molybdenum Cofactor Deficiency Type A (6.4e-05 vs ND), allowing no conclusion about variant significance. c.217C>T has been reported in the literature in homozygote and compound heterozygous individuals affected with Sulfite Oxidase Deficiency Due To Molybdenum Cofactor Deficiency Type A (examples: Reiss_1998, Gumus_2010, Wu_2021). These data indicate that the variant is very likely to 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: 9921896, 20573177, 33840416). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, classifying the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000006495 SCV004193248 pathogenic Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A 2023-10-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV004018578 SCV004980491 uncertain significance Inborn genetic diseases 2022-07-17 criteria provided, single submitter clinical testing The c.217C>T (p.R73W) alteration is located in exon 1 (coding exon 1) of the MOCS1 gene. This alteration results from a C to T substitution at nucleotide position 217, causing the arginine (R) at amino acid position 73 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
OMIM RCV000006495 SCV000026678 pathogenic Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A 2003-06-01 no assertion criteria provided literature only

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