Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000755729 | SCV000883227 | likely pathogenic | Short-rib thoracic dysplasia 20 with polydactyly | 2018-10-15 | criteria provided, single submitter | curation | This variant is interpreted as Likely Pathogenic, for Short-rib thoracic dysplasia 7/20 with polydactyly, digenic. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM3 => For recessive disorders, detected in trans with a pathogenic variant (https://www.ncbi.nlm.nih.gov/pubmed/27158779). PVS1-Moderate => PVS1 downgraded in strength to Moderate. |
Invitae | RCV002532709 | SCV003525707 | uncertain significance | not provided | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln276*) in the INTU gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in INTU cause disease. This variant is present in population databases (rs373900644, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with short-rib polydactyly syndrome (PMID: 27158779). ClinVar contains an entry for this variant (Variation ID: 504483). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
OMIM | RCV000599227 | SCV000710808 | pathogenic | Short-rib thoracic dysplasia 7/20 with polydactyly, digenic | 2018-04-02 | no assertion criteria provided | literature only |