Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001235646 | SCV001408339 | uncertain significance | Legius syndrome | 2023-07-12 | criteria provided, single submitter | clinical testing | 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: 961884). 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. This variant is present in population databases (rs143121426, gnomAD 0.007%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 179 of the SPRED1 protein (p.Glu179Lys). |
| Ambry Genetics | RCV002348794 | SCV002647116 | uncertain significance | Cardiovascular phenotype | 2022-07-27 | criteria provided, single submitter | clinical testing | The p.E179K variant (also known as c.535G>A), located in coding exon 5 of the SPRED1 gene, results from a G to A substitution at nucleotide position 535. The glutamic acid at codon 179 is replaced by lysine, an amino acid with 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. |
| ARUP Laboratories, |
RCV001235646 | SCV003800160 | uncertain significance | Legius syndrome | 2022-04-29 | criteria provided, single submitter | clinical testing | The SPRED1 c.535G>A; p.Glu179Lys variant (rs143121426), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 961884). However, ARUP Laboratories has detected this variant in an individual with an alternative molecular explanation for disease. This variant is only observed on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamic acid at codon 179 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.278). Due to limited information, the clinical significance of the p.Glu179Lys variant is uncertain at this time. |
| Service de Génétique Moléculaire, |
RCV001261131 | SCV001438538 | likely benign | Noonan syndrome | no assertion criteria provided | clinical testing |