Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001972665 | SCV002247263 | pathogenic | not provided | 2023-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 327 of the ALPL protein (p.Phe327Cys). This variant is present in population databases (rs779832611, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of hypophosphatasia (Invitae). This variant is also known as F310C. ClinVar contains an entry for this variant (Variation ID: 1457572). 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%. This variant disrupts the p.Phe327 amino acid residue in ALPL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8954059, 9814472, 12412800, 15660230). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Genome Diagnostics Laboratory, |
RCV002276955 | SCV002564894 | likely pathogenic | Osteogenesis imperfecta | 2022-06-14 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003475237 | SCV004195008 | likely pathogenic | Adult hypophosphatasia | 2023-07-07 | criteria provided, single submitter | clinical testing |