Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667672 | SCV000792158 | uncertain significance | Infantile hypophosphatasia | 2017-06-09 | criteria provided, single submitter | clinical testing | |
| Equipe Genetique des Anomalies du Developpement, |
RCV004017715 | SCV004847189 | pathogenic | Adult hypophosphatasia | 2023-05-02 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586858 | SCV005076434 | pathogenic | Hypophosphatasia | 2024-04-26 | criteria provided, single submitter | clinical testing | Variant summary: ALPL c.1333T>C (p.Ser445Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245852 control chromosomes. c.1333T>C has been reported in the literature in compound heterozygous state with a pathogenic variant or in heterozygous state in individuals affected with infantile or adult form of Hypophosphatasia with moderate ro severe symptom (Sugiyama_2022, del Angel_2020, Zurutuza_1999, Taillandier_2018). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Fauvert_2009). The following publications have been ascertained in the context of this evaluation (PMID: 19500388, 9781036, 35197081, 29236161, 10332035, 32160374). ClinVar contains an entry for this variant (Variation ID: 552418). Based on the evidence outlined above, the variant was classified as pathogenic. |