Submissions for variant NM_025137.4(SPG11):c.1471_1472del (p.Leu491fs)

dbSNP: rs312262727

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000034174	SCV001202580	pathogenic	Hereditary spastic paraplegia 11	2023-12-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu491Aspfs*66) in the SPG11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829). This variant is present in population databases (rs312262727, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 18079167, 27217339). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 41273). For these reasons, this variant has been classified as Pathogenic.
Paris Brain Institute, Inserm - ICM	RCV000034174	SCV001451245	pathogenic	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000034174	SCV002764132	pathogenic	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing
GeneReviews	RCV000034174	SCV000058112	not provided	Hereditary spastic paraplegia 11		no assertion provided	literature only