Submissions for variant NM_176806.4(MOCS2):c.178C>T (p.Arg60Cys)

gnomAD frequency: 0.00045  dbSNP: rs146074751

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000300889	SCV000457871	uncertain significance	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001344244	SCV001538284	uncertain significance	not provided	2025-02-03	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 60 of the MOCS2A protein (p.Arg60Cys). This variant is present in population databases (rs146074751, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MOCS2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 353881). 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 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.
Ambry Genetics	RCV004022000	SCV004979617	likely benign	Inborn genetic diseases	2022-01-14	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Breakthrough Genomics, Breakthrough Genomics	RCV001344244	SCV005189524	uncertain significance	not provided		criteria provided, single submitter	not provided
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000300889	SCV005878425	uncertain significance	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	2023-12-20	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000300889	SCV006056384	uncertain significance	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	2022-06-03	criteria provided, single submitter	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001344244	SCV001743056	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001344244	SCV001968541	uncertain significance	not provided		no assertion criteria provided	clinical testing