Submissions for variant NM_003119.4(SPG7):c.1617del (p.Val540fs)

dbSNP: rs762795756

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000256054	SCV000322297	pathogenic	not provided	2016-08-25	criteria provided, single submitter	clinical testing	The c.1617delC variant in the SPG7 gene has been reported previously in association with hereditary spastic paraplegia in an individual who was homozygous for c.1617delC and an individual who was heterozygous for c.1617delC and a large deletion of the SPG7 gene (Arnoldi et al., 2008; Orsucci et al., 2014). The deletion causes a frameshift starting with codon Valine 540, changes this amino acid to a Cysteine residue and creates a premature Stop codon at position 52 of the new reading frame, denoted p.Val540CysfsX52. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
CeGaT Center for Human Genetics Tuebingen	RCV000256054	SCV001246897	pathogenic	not provided	2017-09-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848041	SCV002105848	pathogenic	Hereditary spastic paraplegia	2021-06-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001855011	SCV002230728	pathogenic	Hereditary spastic paraplegia 7	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val540Cysfs*52) in the SPG7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162). This variant is present in population databases (rs762795756, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 18200586). This variant is also known as c.1616delC (p.Val540fs). ClinVar contains an entry for this variant (Variation ID: 265420). For these reasons, this variant has been classified as Pathogenic.
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV001855011	SCV005044609	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research
OMIM	RCV001855011	SCV000027415	pathogenic	Hereditary spastic paraplegia 7	2008-04-01	no assertion criteria provided	literature only