ClinVar Miner

Submissions for variant NM_152594.3(SPRED1):c.281T>C (p.Ile94Thr) (rs761473300)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433869 SCV000535308 uncertain significance not provided 2017-01-05 criteria provided, single submitter clinical testing The I94T variant in the SPRED1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I94T variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I94T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret I94T as a variant of uncertain significance
Invitae RCV001212405 SCV001383988 uncertain significance Legius syndrome 2019-06-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 94 of the SPRED1 protein (p.Ile94Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs761473300, ExAC 0.001%). This variant has not been reported in the literature in individuals with SPRED1-related conditions. ClinVar contains an entry for this variant (Variation ID: 392095). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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