Submissions for variant NM_025137.4(SPG11):c.5696G>A (p.Arg1899Gln)

gnomAD frequency: 0.00002  dbSNP: rs768303307

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000193609	SCV000249015	uncertain significance	not specified	2015-01-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000642531	SCV000764216	uncertain significance	Hereditary spastic paraplegia 11	2021-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 1899 of the SPG11 protein (p.Arg1899Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs768303307, ExAC 0.02%). 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: 212293). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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-Nilou Lab	RCV002467659	SCV002763802	uncertain significance	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467660	SCV002763803	uncertain significance	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000642531	SCV002763804	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003165438	SCV003893034	uncertain significance	Inborn genetic diseases	2023-02-09	criteria provided, single submitter	clinical testing	The c.5696G>A (p.R1899Q) alteration is located in exon 30 (coding exon 30) of the SPG11 gene. This alteration results from a G to A substitution at nucleotide position 5696, causing the arginine (R) at amino acid position 1899 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect - Invitae Patient Insights Network	RCV003330557	SCV004037552	not provided	Amyotrophic lateral sclerosis type 5; Hereditary spastic paraplegia 11; Charcot-Marie-Tooth disease axonal type 2X		no assertion provided	phenotyping only	Variant classified as Uncertain significance and reported on 02-17-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.