Submissions for variant NM_001358530.2(MOCS1):c.377G>A (p.Gly126Asp)

gnomAD frequency: 0.00006  dbSNP: rs372246702

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000853356	SCV000996232	likely pathogenic	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	2018-12-31	criteria provided, single submitter	clinical testing	This variant has been previously reported as in patients with molybdenum cofactor deficiency (PMID: 9921896). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.006% (14/245472) and thus is presumed to be rare. The c.377G>A (p.Gly126Asp) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.377G>A (p.Gly126Asp) variant is classified as likely pathogenic.
Invitae	RCV000853356	SCV002173523	likely pathogenic	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	2023-12-10	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 126 of the MOCS1 protein (p.Gly126Asp). This variant is present in population databases (rs372246702, gnomAD 0.01%). This missense change has been observed in individuals with molybdenum cofactor deficiency (PMID: 921896, 32014857; Invitae). ClinVar contains an entry for this variant (Variation ID: 692063). 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.
CeGaT Center for Human Genetics Tuebingen	RCV001528779	SCV004032673	likely pathogenic	not provided	2023-08-01	criteria provided, single submitter	clinical testing	MOCS1: PM3:Strong, PM2, PP3
Baylor Genetics	RCV000853356	SCV004193247	likely pathogenic	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528779	SCV001741116	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528779	SCV001957592	likely pathogenic	not provided		no assertion criteria provided	clinical testing