ClinVar Miner

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

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255725 SCV000321947 pathogenic not provided 2016-08-18 criteria provided, single submitter clinical testing The P293S has previously been reported in association with Sanfilippo syndrome A in an individual who also harbored another missense variant in SGSH, and functional analysis of P293S found that it is associated with significantly reduced enzyme activity (Lee-Chen et al., 2002). P293S was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The P293S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, we interpret P293S to be a pathogenic variant.
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 2018-08-15 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.
Counsyl RCV000409289 SCV000486447 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2016-11-12 no assertion criteria provided clinical testing

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