Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002311089 | SCV000319905 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2015-07-24 | criteria provided, single submitter | clinical testing | The p.L209M variant (also known as c.625C>A), located in coding exon 1 of the SKI gene, results from a C to A substitution at nucleotide position 625. The leucine at codon 209 is replaced by methionine, an amino acid with highly similar properties. 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 6343 samples (12686 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Gene |
RCV002466482 | SCV002762266 | uncertain significance | not provided | 2022-12-05 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
Invitae | RCV003517163 | SCV004277201 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 209 of the SKI protein (p.Leu209Met). This variant is present in population databases (rs771298442, gnomAD 0.006%). 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: 264172). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SKI protein function. 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. |
ARUP Laboratories, |
RCV003517163 | SCV004564297 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-05-01 | criteria provided, single submitter | clinical testing | The SKI c.625C>A; p.Leu209Met variant (rs771298442), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 264172). This variant is observed in the general population with an overall allele frequency of 0.003% (7/262826 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.285). Due to limited information, the clinical significance of this variant is uncertain at this time. |