ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.1040A>G (p.Lys347Arg)

dbSNP: rs2089342939
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001041100 SCV001204696 likely pathogenic Mucopolysaccharidosis, MPS-II 2019-12-11 criteria provided, single submitter clinical testing This variant disrupts the p.Lys347 amino acid residue in IDS. Other variant(s) that disrupt this residue have been observed in individuals with IDS-related conditions (PMID: 11731225, 9266380, 8940265, 9222763, 15614569), which suggests that this may be a clinically significant amino acid residue. 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. 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"). This variant has been observed in an individual affected with mucopolysaccharidosis type II (PMID: 27883178). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 347 of the IDS protein (p.Lys347Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV001041100 SCV005089409 likely pathogenic Mucopolysaccharidosis, MPS-II 2024-06-07 criteria provided, single submitter literature only Located in a mutational hot spot and/or critical functional domain (PM1_Moderate), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Missense change at the same amino acid residue as a pathogenic variant (PM5_Moderate), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate)

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