Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001046425 | SCV001210329 | pathogenic | Juvenile polyposis syndrome | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the BMPR1A mRNA. The next in-frame methionine is located at codon 29. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with clinical features of juvenile polyposis syndrome (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 843741). While this variant is expected to result in an absent protein product, possible rescue of translational initiation by the downstream methionine would lead to the disruption of the signal peptide (residues 1-23), which is important for BMPR1A-mediated cellular localization (PMID: 23433720). For these reasons, this variant has been classified as Pathogenic. |