ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1000C>T (p.Pro334Ser)

gnomAD frequency: 0.00003  dbSNP: rs775433131
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198950 SCV000250674 uncertain significance not provided 2023-05-31 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 RCV000539809 SCV000637270 uncertain significance Shprintzen-Goldberg syndrome 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 334 of the SKI protein (p.Pro334Ser). This variant is present in population databases (rs775433131, 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: 213688). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SKI protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002336532 SCV002634900 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-05 criteria provided, single submitter clinical testing The p.P334S variant (also known as c.1000C>T), located in coding exon 2 of the SKI gene, results from a C to T substitution at nucleotide position 1000. The proline at codon 334 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, serine is the reference amino acid in other 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 alteration remains unclear.

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