ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.641T>C (p.Leu214Pro)

gnomAD frequency: 0.00001  dbSNP: rs771810111
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000690528 SCV000818215 pathogenic Mucopolysaccharidosis, MPS-IV-A 2023-03-10 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 24726177). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs771810111, gnomAD 0.005%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 214 of the GALNS protein (p.Leu214Pro). ClinVar contains an entry for this variant (Variation ID: 569811). For these reasons, this variant has been classified as Pathogenic. 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 GALNS protein function.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000690528 SCV001547760 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter curation In vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; PS3_supporting); very low frequency in gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting)
Genome-Nilou Lab RCV000690528 SCV002044992 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-11-07 criteria provided, single submitter clinical testing

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