ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.3074A>T (p.Lys1025Ile)

dbSNP: rs1567163203
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001043412 SCV001207158 uncertain significance Hereditary spastic paraplegia 11 2022-09-06 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 1025 of the SPG11 protein (p.Lys1025Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 841229). 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: "Deleterious"; 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.
Ambry Genetics RCV002319652 SCV002608672 uncertain significance Inborn genetic diseases 2020-03-19 criteria provided, single submitter clinical testing The p.K1025I variant (also known as c.3074A>T), located in coding exon 17 of the SPG11 gene, results from an A to T substitution at nucleotide position 3074. The lysine at codon 1025 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. 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.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV001043412 SCV002768390 uncertain significance Hereditary spastic paraplegia 11 2020-05-25 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v0.6.1, this variant is classified as 3B-VUS. Following criteria are met: 0102 - Loss of function is a known mechanism of disease for this gene. 0106 - This gene is known to be associated with autosomal recessive disease. 0200 - Variant is predicted to result in a missense amino acid change from lysine to isoleucine (exon 17). 0301 - Variant is absent from gnomAD. 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. 0604 - Variant is not located in an established domain, motif or hotspot. 0705 - No comparable variants in relevant codon/region have previous evidence for pathogenicity. 0807 - Variant has not previously been reported in a clinical context. 0905 - No published segregation evidence has been identified for this variant. 1007 - No published functional evidence has been identified for this variant.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.