Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001293360 | SCV001481815 | likely pathogenic | Intellectual disability | 2021-02-25 | criteria provided, single submitter | clinical testing | The variant chr17-78188504-G-A, SGSH(NM_000199.5):c.416C>T,p.(Thr139Met) was identified in an individual with NDD. Inheritance was not applicable (heterozygous). The variant was reviewed according to current ACMG recommendations and classified as Likely Pathogenic (criteria: PM2_Supporting, PM3_Strong, PP3_Supporting, PP4_Supporting). This variant was identified in a compound heterozygous state with the variantNM_000199.5(SGSH):c.267C>A (p.Tyr89Ter) ( Variation ID: 983123). |
Genome- |
RCV000666794 | SCV002045105 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000666794 | SCV002060236 | uncertain significance | Mucopolysaccharidosis, MPS-III-A | 2021-11-12 | criteria provided, single submitter | clinical testing | NM_000199.3(SGSH):c.416C>T(T139M) is a missense variant classified as a variant of uncertain significance in the context of mucopolysaccharidosis type IIIA. T139M has been observed in cases with relevant disease (PMID: 9285796; 24576347). Functional assessments of this variant are not available in the literature. T139M has been observed in population frequency databases (gnomAD: AFR 0.01%). In summary, there is insufficient evidence to classify NM_000199.3(SGSH):c.416C>T(T139M) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Invitae | RCV000666794 | SCV003443328 | uncertain significance | Mucopolysaccharidosis, MPS-III-A | 2022-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 139 of the SGSH protein (p.Thr139Met). This variant is present in population databases (rs775112689, gnomAD 0.004%). This missense change has been observed in individual(s) with Sanfilippo syndrome (PMID: 9285796, 24576347). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 551670). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000666794 | SCV004100649 | uncertain significance | Mucopolysaccharidosis, MPS-III-A | criteria provided, single submitter | clinical testing | The missense variant p.T139M in SGSH (NM_000199.5) has been submitted previously to ClinVar with conflicting interpretations of pathogenicity (Likely Pathogenic/ Uncertain Significance). No details for independent assesment are available for the Likely Pathogenic classification. It has not been reported previously in affected individuals to the best of our knowledge. The p.T139M variant is observed in 1/16,194 (0.0062%) alleles from individuals of African background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes.The p.T139M missense variant is predicted to be damaging by both SIFT and PolyPhen2. The threonine residue at codon 139 of SGSH is conserved in all mammalian species. The nucleotide c.416 in SGSH is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. | |
Baylor Genetics | RCV000666794 | SCV004201089 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2023-09-20 | criteria provided, single submitter | clinical testing | |
Section for Clinical Neurogenetics, |
RCV000666794 | SCV001156105 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2019-08-01 | no assertion criteria provided | research |