ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.2321A>C (p.Glu774Ala)

gnomAD frequency: 0.00001  dbSNP: rs566318835
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001848185 SCV002105685 uncertain significance Hereditary spastic paraplegia 2017-05-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001885408 SCV002275930 uncertain significance Hereditary spastic paraplegia 11 2022-08-10 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 774 of the SPG11 protein (p.Glu774Ala). This variant is present in population databases (rs566318835, gnomAD 0.004%). This missense change has been observed in individual(s) with developmental disorders (PMID: 32005694). ClinVar contains an entry for this variant (Variation ID: 1344082). 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: "Possibly 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 RCV002458635 SCV002735707 uncertain significance Inborn genetic diseases 2020-09-15 criteria provided, single submitter clinical testing The p.E774A variant (also known as c.2321A>C), located in coding exon 13 of the SPG11 gene, results from an A to C substitution at nucleotide position 2321. The glutamic acid at codon 774 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV002468331 SCV002764064 uncertain significance Amyotrophic lateral sclerosis type 5 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468332 SCV002764065 uncertain significance Charcot-Marie-Tooth disease axonal type 2X criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001885408 SCV002764066 uncertain significance Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing

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.