ClinVar Miner

Submissions for variant NM_152594.3(SPRED1):c.1301G>T (p.Gly434Val)

gnomAD frequency: 0.00001  dbSNP: rs746414913
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521434 SCV000621882 uncertain significance not provided 2020-11-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
New York Genome Center RCV001836835 SCV002097744 uncertain significance Legius syndrome 2021-01-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV003159694 SCV003868992 uncertain significance Cardiovascular phenotype 2022-12-23 criteria provided, single submitter clinical testing The p.G434V variant (also known as c.1301G>T), located in coding exon 7 of the SPRED1 gene, results from a G to T substitution at nucleotide position 1301. The glycine at codon 434 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is conserved. 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.
Invitae RCV001836835 SCV004549330 uncertain significance Legius syndrome 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 434 of the SPRED1 protein (p.Gly434Val). This variant is present in population databases (rs746414913, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SPRED1-related conditions. ClinVar contains an entry for this variant (Variation ID: 453028). 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 SPRED1 protein function with a negative predictive value of 80%. 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.

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