Submissions for variant NM_025137.4(SPG11):c.5315G>A (p.Arg1772His)

gnomAD frequency: 0.00016  dbSNP: rs150823040

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000541207	SCV000642249	likely benign	Hereditary spastic paraplegia 11	2023-12-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000541207	SCV001279294	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848946	SCV002105732	uncertain significance	Hereditary spastic paraplegia	2020-10-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467874	SCV002763839	uncertain significance	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467875	SCV002763841	uncertain significance	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000541207	SCV002763842	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing
GeneDx	RCV002509426	SCV002818985	uncertain significance	not provided	2022-12-29	criteria provided, single submitter	clinical testing	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; This variant is associated with the following publications: (PMID: 26556829)
Ambry Genetics	RCV003372748	SCV004062445	uncertain significance	Inborn genetic diseases	2023-06-28	criteria provided, single submitter	clinical testing	The c.5315G>A (p.R1772H) 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 5315, causing the arginine (R) at amino acid position 1772 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic	RCV002509426	SCV005409909	uncertain significance	not provided	2024-03-07	criteria provided, single submitter	clinical testing