Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001067182 | SCV001232228 | pathogenic | not provided | 2023-09-22 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 95 of the ALPL protein (p.Val95Met). This variant is present in population databases (rs139811782, gnomAD 0.01%). This missense change has been observed in individual(s) with hypophosphatasia (PMID: 30719581, 31641588). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 427763). Experimental studies have shown that this missense change affects ALPL function (PMID: 32160374). For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV001535923 | SCV001752575 | likely pathogenic | Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia | 2021-06-30 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001580504 | SCV001810260 | likely pathogenic | Childhood hypophosphatasia | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV002279265 | SCV002564739 | uncertain significance | Osteogenesis imperfecta | 2022-02-28 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003470594 | SCV004194474 | likely pathogenic | Adult hypophosphatasia | 2023-09-11 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000490714 | SCV000579348 | likely pathogenic | Low alkaline phosphatase | no assertion criteria provided | clinical testing | ||
Natera, |
RCV001273158 | SCV001455763 | uncertain significance | Hypophosphatasia | 2020-09-16 | no assertion criteria provided | clinical testing |