Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001974856 | SCV002214405 | pathogenic | not provided | 2023-04-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg184 amino acid residue in ALPL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9781036, 19500388). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects ALPL function (PMID: 32160374). 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. ClinVar contains an entry for this variant (Variation ID: 1439050). This missense change has been observed in individual(s) with hypophosphatasia (PMID: 30555565, 32160374). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 184 of the ALPL protein (p.Arg184Gln). |
Fulgent Genetics, |
RCV002507646 | SCV002808573 | pathogenic | Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia | 2021-07-29 | criteria provided, single submitter | clinical testing |