Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002311190 | SCV000320439 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2015-11-10 | criteria provided, single submitter | clinical testing | The c.249_251dupGCC variant (also known as p.P84dup), located in coding exon 1 of the SKI gene, results from an in-frame duplication of GCC between nucleotide positions 249 and 251. This results in the duplication of an extra proline residue between codons 84 and 85. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6293 samples (12586 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV003517164 | SCV004277261 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-12-19 | criteria provided, single submitter | clinical testing | This variant, c.249_251dup, results in the insertion of 1 amino acid(s) of the SKI protein (p.Pro84dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SKI-related conditions. ClinVar contains an entry for this variant (Variation ID: 264471). 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. |