ClinVar Miner

Submissions for variant NM_152594.3(SPRED1):c.1006G>A (p.Val336Ile)

gnomAD frequency: 0.00005  dbSNP: rs373477920
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493530 SCV000582542 uncertain significance not provided 2017-05-15 criteria provided, single submitter clinical testing The V336I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge; however, it was observed to co-occur in a patient tested at GeneDx with another known pathogenic variant. The V336I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V336I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species and Isoleucine is present many species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000819475 SCV000960139 uncertain significance Legius syndrome 2023-09-08 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 336 of the SPRED1 protein (p.Val336Ile). This variant is present in population databases (rs373477920, gnomAD 0.02%). 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: 429870). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt SPRED1 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.
Ambry Genetics RCV002420259 SCV002729858 uncertain significance Cardiovascular phenotype 2021-10-29 criteria provided, single submitter clinical testing The p.V336I variant (also known as c.1006G>A), located in coding exon 7 of the SPRED1 gene, results from a G to A substitution at nucleotide position 1006. The valine at codon 336 is replaced by isoleucine, an amino acid with highly similar 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.

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