ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.877C>T (p.Pro293Ser) (rs143947056)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255725 SCV000321947 pathogenic not provided 2021-08-10 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect due to a significant reduction of enzyme activity (Lee-Chen et al., 2002); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12000360, 26787381, 22976768, 29930972, 30070758, 31589614, 24816101, 25807448)
SIB Swiss Institute of Bioinformatics RCV000409289 SCV000803563 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Mucopolysaccharidosis type IIIA (Sanfilippo A), in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 => Well-established functional studies show a deleterious effect (PMID:12000360).
Fulgent Genetics,Fulgent Genetics RCV000409289 SCV000893481 pathogenic Mucopolysaccharidosis, MPS-III-A 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000409289 SCV000963680 pathogenic Mucopolysaccharidosis, MPS-III-A 2020-09-24 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 293 of the SGSH protein (p.Pro293Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs143947056, ExAC 0.006%). This variant has been observed in combination with another SGSH variant in individuals affected with mucopolysaccharidosis type III (PMID: 22976768, 26787381, 12000360, Invitae). ClinVar contains an entry for this variant (Variation ID: 265258). Experimental studies have shown that this missense change results in a SGSH protein with minimal enzymatic activity (PMID: 12000360). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001266815 SCV001444994 pathogenic Inborn genetic diseases 2014-09-07 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV000409289 SCV002045494 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2021-11-07 criteria provided, single submitter clinical testing
Counsyl RCV000409289 SCV000486447 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2016-11-12 no assertion criteria provided clinical testing
Natera, Inc. RCV000409289 SCV001463878 pathogenic Mucopolysaccharidosis, MPS-III-A 2020-09-16 no assertion criteria provided clinical testing

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