Submissions for variant NM_014946.4(SPAST):c.746C>G (p.Ser249Ter)

dbSNP: rs1553314902

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000713472	SCV000844084	pathogenic	not provided	2018-04-03	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000713472	SCV001446616	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001849079	SCV002105643	pathogenic	Hereditary spastic paraplegia	2018-04-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002532955	SCV003524202	pathogenic	Hereditary spastic paraplegia 4	2022-10-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser249*) in the SPAST gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPAST are known to be pathogenic (PMID: 20932283). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 12124993). ClinVar contains an entry for this variant (Variation ID: 586665). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000713472	SCV005050611	pathogenic	not provided	2024-05-01	criteria provided, single submitter	clinical testing	SPAST: PVS1, PM2, PS4:Supporting