Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000779692 | SCV000916443 | likely pathogenic | Hypophosphatasia | 2018-08-20 | criteria provided, single submitter | clinical testing | Variant summary: ALPL c.1182dupT (p.Ile395TyrfsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4.1e-06 in 246234 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1182dupT in individuals affected with Hypophosphatasia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV001055790 | SCV001220199 | pathogenic | not provided | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ile395Tyrfs*10) in the ALPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALPL are known to be pathogenic (PMID: 3174660, 10679946, 32973344, 33814268). This variant is present in population databases (rs754826836, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ALPL-related conditions. ClinVar contains an entry for this variant (Variation ID: 632629). For these reasons, this variant has been classified as Pathogenic. |
| Centre for Mendelian Genomics, |
RCV001198564 | SCV001369553 | likely pathogenic | Adult hypophosphatasia | 2019-09-05 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5. |
| Johns Hopkins Genomics, |
RCV001281691 | SCV001469054 | pathogenic | Childhood hypophosphatasia | 2020-12-02 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001198564 | SCV004194941 | likely pathogenic | Adult hypophosphatasia | 2023-07-25 | criteria provided, single submitter | clinical testing |