Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000793006 | SCV000932339 | uncertain significance | Legius syndrome | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 430 of the SPRED1 protein (p.Gly430Ala). This variant is present in population databases (rs749389617, 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: 640062). 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 with a negative predictive value of 95%. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797795 | SCV002041833 | uncertain significance | not specified | 2021-11-15 | criteria provided, single submitter | clinical testing | Variant summary: SPRED1 c.1289G>C (p.Gly430Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251136 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1289G>C has been reported in the literature in one individual by a study reviewing all identified SPRED1 mutations, without case-specific information provided (Brems_2012). This report does not provide unequivocal conclusions about association of the variant with Neurofibromatosis Type 1-Like Syndrome (Legius Syndrome). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |