ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.104T>C (p.Leu35Pro)

gnomAD frequency: 0.00004  dbSNP: rs1246249632
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001305508 SCV001494845 likely pathogenic Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V 2023-07-28 criteria provided, single submitter clinical testing This variant disrupts the p.Leu35 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been observed in individuals with NAGLU-related conditions (PMID: 11153910), 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. ClinVar contains an entry for this variant (Variation ID: 1008207). 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 NAGLU protein function. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 35 of the NAGLU protein (p.Leu35Pro). This missense change has been observed in individual(s) with MPS III (Invitae).

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