Total submissions: 3
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, |
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 |