ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.629G>A (p.Trp210Ter) (rs886041370)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674194 SCV000799486 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2018-04-19 criteria provided, single submitter clinical testing
GeneDx RCV000345601 SCV000329885 pathogenic not provided 2016-09-01 criteria provided, single submitter clinical testing The W210X variant in the SGSH gene has been reported previously in one individual with MPS Type IIIA in whom a second pathogenic SGSH variant was not identified (Weber et al., 1997). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W210X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret W210X as a pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000674194 SCV000920202 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2018-06-01 criteria provided, single submitter clinical testing Variant summary: SGSH c.629G>A (p.Trp210X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.697C>T (p.Arg233X) and c.1027dupC (p.Leu343fsX159)). The variant was absent in 238874 control chromosomes (gnomAD). The variant, c.629G>A, has been reported in the literature in an individual affected with Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome A)(Weber_1997). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as likely pathogenic.

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