Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Muenke lab, |
RCV000656536 | SCV000778549 | pathogenic | Holoprosencephaly 3 | 2017-03-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002298721 | SCV002588064 | likely pathogenic | not provided | 2022-10-25 | criteria provided, single submitter | clinical testing | Reported in an individual with alobar holoprosencephaly and a complex heart defect and in another individual with holoprosencephaly and a single central incisor. Variant was inherited for both individuals; no clinical information was provided for the parents (Tekendo-Ngongang et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation, as the last 27 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 32022405) |
Labcorp Genetics |
RCV000656536 | SCV003031525 | pathogenic | Holoprosencephaly 3 | 2023-06-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SHH protein. Other variant(s) that disrupt this region (p.Q437*) have been observed in individuals with SHH-related conditions (PMID: 15942944). This suggests that this may be a clinically significant region of the protein. ClinVar contains an entry for this variant (Variation ID: 545579). This premature translational stop signal has been observed in individuals with holoprosencephaly (PMID: 32022405). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser436*) in the SHH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acid(s) of the SHH protein. |