Submissions for variant NM_025137.4(SPG11):c.3425C>G (p.Ser1142Cys)

gnomAD frequency: 0.00005  dbSNP: rs201082396

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000462305	SCV000545208	likely benign	Hereditary spastic paraplegia 11	2024-01-31	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765212	SCV000896448	uncertain significance	Amyotrophic lateral sclerosis type 5; Hereditary spastic paraplegia 11; Charcot-Marie-Tooth disease axonal type 2X	2022-05-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000462305	SCV001277237	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.
UM ALS/MND Lab, University Of Malta	RCV001260216	SCV001437185	uncertain significance	Amyotrophic lateral sclerosis	2020-09-09	criteria provided, single submitter	case-control
Mayo Clinic Laboratories, Mayo Clinic	RCV001508758	SCV001715107	uncertain significance	not provided	2019-04-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848803	SCV002105704	uncertain significance	Hereditary spastic paraplegia	2021-03-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001508758	SCV002520103	uncertain significance	not provided	2022-05-02	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
Genome-Nilou Lab	RCV002467814	SCV002763980	uncertain significance	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467815	SCV002763981	uncertain significance	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000462305	SCV002763982	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003401464	SCV004104037	uncertain significance	SPG11-related disorder	2023-01-13	criteria provided, single submitter	clinical testing	The SPG11 c.3425C>G variant is predicted to result in the amino acid substitution p.Ser1142Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-44900670-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Breakthrough Genomics, Breakthrough Genomics	RCV001508758	SCV005193766	uncertain significance	not provided		criteria provided, single submitter	not provided