ClinVar Miner

Submissions for variant NM_001358530.2(MOCS1):c.1150G>A (p.Glu384Lys) (rs751603831)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000642133 SCV000763786 uncertain significance Molybdenum cofactor deficiency, complementation group A 2017-08-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 384 of the MOCS1 protein (p.Gly384Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in combination with another MOCS1 variant in an individual affected with molybdenum cofactor deficiency (PMID: 9921896). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Illumina Clinical Services Laboratory,Illumina RCV000642133 SCV000916139 uncertain significance Molybdenum cofactor deficiency, complementation group A 2017-09-06 criteria provided, single submitter clinical testing The MOCS1 c.1150G>A (p.Gly384Ser) missense variant has been reported in one study and is found in a compound heterozygous state in one individual with molybdenum cofactor deficiency (Reiss et al. 1998). The p.Gly384Ser variant was absent from 50 control chromosomes and is reported at a frequency of 0.000067 in the European (non-Finnish) population of the Genome Aggregation Database, but this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Expression analysis in E. coli found the p.Gly384Ser variant to have significantly reduced activity compared to wildtype (Hänzelmann et al. 2002). The p.Gly384 residue is conserved across mammals, plants, and bacteria (Reiss et al. 1998). Based on the evidence, the p.Gly384Ser variant is classified as a variant of unknown significance but suspicious for pathogenicity for molybdenum cofactor deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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