ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.1130G>T (p.Arg377Leu) (rs746037899)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633455 SCV000754684 uncertain significance Mucopolysaccharidosis, MPS-III-A 2017-08-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 377 of the SGSH protein (p.Arg377Leu). 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 been reported as homozygous or in combination with another SGSH variant in two individuals affected with mucopolysaccharidosis type III (PMID: 22976768, 25807448). This variant has also been observed on the opposite chromosome (in trans) from another pathogenic variant in an individual affected with this condition (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Algorithms developed to predict the effect of missense changes on protein structure and function 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.

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