Submissions for variant NM_025137.4(SPG11):c.993C>T (p.Ser331=)

gnomAD frequency: 0.00519  dbSNP: rs76823973

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000465378	SCV000391309	benign	Hereditary spastic paraplegia 11	2018-01-12	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000465378	SCV000557279	benign	Hereditary spastic paraplegia 11	2025-02-02	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001288001	SCV001474779	benign	not specified	2020-07-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001579587	SCV001888221	benign	not provided	2019-05-24	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848656	SCV002105789	benign	Hereditary spastic paraplegia	2021-11-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467746	SCV002764185	benign	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467747	SCV002764186	benign	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000465378	SCV002764187	benign	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001579587	SCV005290573	benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579587	SCV001807809	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001288001	SCV001925211	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003930355	SCV004743537	benign	SPG11-related disorder	2019-04-08	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).