Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674648 | SCV000800022 | uncertain significance | Infantile hypophosphatasia | 2018-05-21 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003558529 | SCV004291746 | likely pathogenic | not provided | 2022-11-09 | criteria provided, single submitter | clinical testing | 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 missense change affects ALPL function (PMID: 19500388). 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: 558387). This missense change has been observed in individual(s) with autosomal dominant hypophosphatasia (PMID: 19500388, 25731960). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 429 of the ALPL protein (p.Glu429Lys). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004800532 | SCV005423610 | likely pathogenic | Hypophosphatasia | 2024-10-01 | criteria provided, single submitter | clinical testing | Variant summary: ALPL c.1285G>A (p.Glu429Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251342 control chromosomes (gnomAD). c.1285G>A has been reported in the literature in heterozygous individuals affected with autosomal dominant Odonto hypophosphatasia (examples: Fauvert_2009, Martins_2013, Whyte_2015). These data indicate that the variant is associated with disease. In functional studies, the variant showed reduced residual activity compared to wild-type (example: Fauvert_2009). The following publications have been ascertained in the context of this evaluation (PMID: 19500388, 23791648, 25731960). ClinVar contains an entry for this variant (Variation ID: 558387). Based on the evidence outlined above, the variant was classified as likely pathogenic. |