ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.1400T>C (p.Met467Thr)

dbSNP: rs763073466
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001196910 SCV001367544 uncertain significance Adult hypophosphatasia 2020-01-08 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PP2,PP3,PP5.
Labcorp Genetics (formerly Invitae), Labcorp RCV002560228 SCV003523181 likely pathogenic not provided 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 467 of the ALPL protein (p.Met467Thr). This variant is present in population databases (rs763073466, gnomAD 0.003%). This missense change has been observed in individual(s) with hypophosphatasia (PMID: 34154874). ClinVar contains an entry for this variant (Variation ID: 930908). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ALPL protein function with a positive predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV005021490 SCV005646820 likely pathogenic Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2024-06-15 criteria provided, single submitter clinical testing

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