ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.931G>A (p.Glu311Lys)

gnomAD frequency: 0.00001  dbSNP: rs763457259
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001974667 SCV002216019 pathogenic not provided 2024-01-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 311 of the ALPL protein (p.Glu311Lys). This variant is present in population databases (rs763457259, gnomAD 0.004%). This missense change has been observed in individual(s) with hypophosphatasia (PMID: 12815606, 25731960). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as E294K. ClinVar contains an entry for this variant (Variation ID: 1436006). 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 ALPL protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002243489 SCV002512240 likely pathogenic Infantile hypophosphatasia 2022-02-08 criteria provided, single submitter clinical testing ACMG classification criteria: PS4 supporting, PM2 moderate, PM3 strong, PP3 supporting
Baylor Genetics RCV003464266 SCV004193239 likely pathogenic Adult hypophosphatasia 2023-03-09 criteria provided, single submitter clinical testing

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