Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001378581 | SCV001576183 | likely pathogenic | not provided | 2021-07-21 | criteria provided, single submitter | clinical testing | This variant is also known as N153D. This variant has been observed in individual(s) with hypophosphatasia (PMID: 9781036). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with aspartic acid at codon 170 of the ALPL protein (p.Asn170Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. ClinVar contains an entry for this variant (Variation ID: 1067343). 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. Experimental studies have shown that this variant affects ALPL protein function (PMID: 11802776). 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. |
Baylor Genetics | RCV003469635 | SCV004194330 | likely pathogenic | Adult hypophosphatasia | 2023-10-04 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001826142 | SCV002094058 | likely pathogenic | Hypophosphatasia | 2021-07-07 | no assertion criteria provided | clinical testing |