Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665964 | SCV000790185 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2017-03-17 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000665964 | SCV000893480 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2021-08-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000665964 | SCV000957485 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2024-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 433 of the SGSH protein (p.Arg433Trp). This variant is present in population databases (rs777267343, gnomAD 0.009%). This missense change has been observed in individual(s) with mucopolysaccharidosis type IIIB (PMID: 11182930, 15542396, 29023963). ClinVar contains an entry for this variant (Variation ID: 551014). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SGSH protein function. Experimental studies have shown that this missense change affects SGSH function (PMID: 15542396). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000665964 | SCV001361816 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2019-07-05 | criteria provided, single submitter | clinical testing | Variant summary: SGSH c.1297C>T (p.Arg433Trp) results in a non-conservative amino acid change located in a domain of unknown function, DUF4976 (IPR032506) 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 2e-05 in 250408 control chromosomes (gnomAD). The variant, c.1297C>T, has been reported in the literature in homozygosity or in compound heterozygous state in multiple individuals affected with Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome A) (e.g. Beesley_2000, Chabas_2001, Heron_2011, Pollard_2013). These data indicate that the variant is very likely to be associated with disease. Publications reported no significant sulfamidase activity in fibroblasts from a homozygous patient (Montfort_2004), and in transiently transfected mammalian cells (Muschol_2004). Two ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely pathogenic (1x) and pathogenic (1x). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Genome- |
RCV000665964 | SCV002045483 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002293469 | SCV002586588 | pathogenic | not provided | 2024-03-14 | criteria provided, single submitter | clinical testing | Published functional studies found this variant is associated with significantly reduced enzyme activity (PMID: 15542396); Not observed at significant frequency in large population cohorts (gnomAD); 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: 24816101, 25807448, 11182930, 11343308, 22976768, 15146460, 21204211, 34991944, 15542396, 29023963) |
| Baylor Genetics | RCV000665964 | SCV004201112 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-07-18 | criteria provided, single submitter | clinical testing |