ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.971G>T (p.Gly324Val) (rs398123125)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000078005 SCV000109843 pathogenic not provided 2014-01-07 criteria provided, single submitter clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV000677616 SCV000803134 likely pathogenic Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Very low frequencyin GnomAD (PM2); Reputable source identifies as pathogenic (PP5)
Invitae RCV000677616 SCV000835529 likely pathogenic Mucopolysaccharidosis type 6 2018-09-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 324 of the ARSB protein (p.Gly324Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another ARSB variant in individuals affected with mucopolysaccharidosis type VI (PMID: 17458871, 23557332, Invitae). ClinVar contains an entry for this variant (Variation ID: 92356). Experimental studies have shown that this variant can cause reduced ARSB protein expression in vitro (PMID: 23557332). 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 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.
Ambry Genetics RCV001266364 SCV001444538 pathogenic Inborn genetic diseases 2018-05-18 criteria provided, single submitter clinical testing

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