ClinVar Miner

Submissions for variant NM_002076.4(GNS):c.1063C>T (p.Arg355Ter)

dbSNP: rs119461974
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000003066 SCV002231729 pathogenic Mucopolysaccharidosis, MPS-III-D 2022-11-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2932). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 12573255). This variant is present in population databases (rs119461974, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg355*) in the GNS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNS are known to be pathogenic (PMID: 20232353).
GeneDx RCV003314547 SCV004014292 pathogenic not provided 2023-01-11 criteria provided, single submitter clinical testing Multiple functional studies performed using patient-derived cell lines demonstrated no N-acetylglucosamine 6-sulfatase activity in cells homozygous for this variant (Pierzynowska et al., 2020; Wang et al., 2021; Gaffke et al., 2022); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 32944950, 12573255, 34928474, 33195185, 33320673, 32366041, 34828358)
OMIM RCV000003066 SCV000023224 pathogenic Mucopolysaccharidosis, MPS-III-D 2003-01-01 no assertion criteria provided literature only

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