Submissions for variant NM_025137.4(SPG11):c.3988C>G (p.Gln1330Glu)

gnomAD frequency: 0.00025  dbSNP: rs375363608

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000168212	SCV000218878	uncertain significance	Hereditary spastic paraplegia 11	2022-08-12	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1330 of the SPG11 protein (p.Gln1330Glu). This variant is present in population databases (rs375363608, gnomAD 0.03%). 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: 188249). 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.
Illumina Laboratory Services, Illumina	RCV000168212	SCV000391287	uncertain significance	Hereditary spastic paraplegia 11	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Athena Diagnostics	RCV000993047	SCV001145749	uncertain significance	not provided	2018-09-20	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000993047	SCV001715105	uncertain significance	not provided	2021-02-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000993047	SCV001961497	uncertain significance	not provided	2023-12-01	criteria provided, single submitter	clinical testing	SPG11: PM2, BP4
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847792	SCV002105712	uncertain significance	Hereditary spastic paraplegia	2019-03-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002372053	SCV002625561	uncertain significance	Inborn genetic diseases	2022-08-17	criteria provided, single submitter	clinical testing	The p.Q1330E variant (also known as c.3988C>G), located in coding exon 23 of the SPG11 gene, results from a C to G substitution at nucleotide position 3988. The glutamine at codon 1330 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly 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.
Genome-Nilou Lab	RCV002467641	SCV002763942	uncertain significance	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467642	SCV002763943	uncertain significance	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000168212	SCV002763944	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000993047	SCV003820038	uncertain significance	not provided	2020-12-16	criteria provided, single submitter	clinical testing