Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000665315 | SCV000789415 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2017-02-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000665315 | SCV001362833 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2019-11-15 | criteria provided, single submitter | clinical testing | Variant summary: SGSH c.268G>A (p.Gly90Arg) results in a non-conservative amino acid change located in the Sulfatase, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 248612 control chromosomes (gnomAD). c.268G>A has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome A)(Bunge_1997, Sun_2011, Heron_2011, Chistiakov_2014). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000665315 | SCV001372574 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-09-08 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs774010006, gnomAD 0.006%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 90 of the SGSH protein (p.Gly90Arg). This missense change has been observed in individual(s) with clinical features of SGSH-related conditions (PMID: 21204211, 21455105, 24875751). ClinVar contains an entry for this variant (Variation ID: 550542). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SGSH protein function. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000665315 | SCV002045506 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000665315 | SCV004201097 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-09-09 | criteria provided, single submitter | clinical testing |