Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000690176 | SCV000817855 | uncertain significance | Legius syndrome | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 428 of the SPRED1 protein (p.Arg428His). This variant is present in population databases (rs369492789, gnomAD 0.006%). 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: 569525). 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. |
Gene |
RCV001756174 | SCV001986456 | uncertain significance | not provided | 2021-03-18 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002386187 | SCV002691259 | uncertain significance | Cardiovascular phenotype | 2021-10-01 | criteria provided, single submitter | clinical testing | The p.R428H variant (also known as c.1283G>A), located in coding exon 7 of the SPRED1 gene, results from a G to A substitution at nucleotide position 1283. The arginine at codon 428 is replaced by histidine, 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. |