ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.3538C>A (p.Pro1180Thr)

gnomAD frequency: 0.00001  dbSNP: rs747910594
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000642544 SCV000764230 uncertain significance Hereditary spastic paraplegia 11 2022-03-03 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1180 of the SPG11 protein (p.Pro1180Thr). This variant is present in population databases (rs747910594, gnomAD 0.002%). 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: 534849). 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001849017 SCV002105705 uncertain significance Hereditary spastic paraplegia 2017-02-24 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467952 SCV002763974 uncertain significance Amyotrophic lateral sclerosis type 5 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467953 SCV002763975 uncertain significance Charcot-Marie-Tooth disease axonal type 2X criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000642544 SCV002763976 uncertain significance Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing
GeneDx RCV003153782 SCV003842512 uncertain significance not provided 2022-09-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003258902 SCV003967509 uncertain significance Inborn genetic diseases 2023-04-18 criteria provided, single submitter clinical testing The c.3538C>A (p.P1180T) alteration is located in exon 21 (coding exon 21) of the SPG11 gene. This alteration results from a C to A substitution at nucleotide position 3538, causing the proline (P) at amino acid position 1180 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.