ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.734G>T (p.Arg245Leu) (rs104894635)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD, LLC RCV000179273 SCV000231495 uncertain significance not provided 2015-05-06 criteria provided, single submitter clinical testing
Invitae RCV001376860 SCV001574046 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2020-09-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 245 of the SGSH protein (p.Arg245Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SGSH-related conditions. ClinVar contains an entry for this variant (Variation ID: 198058). 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. This variant disrupts the p.Arg245 amino acid residue in SGSH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9158154, 9700599, 15146460, 10601282). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Nilou-Genome Lab RCV001376860 SCV002045098 uncertain significance Mucopolysaccharidosis, MPS-III-A 2021-11-07 criteria provided, single submitter clinical testing

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