Submissions for variant NM_003119.4(SPG7):c.1A>G (p.Met1Val)

gnomAD frequency: 0.00001  dbSNP: rs794726906

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000173302	SCV000224400	likely pathogenic	not provided	2015-04-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000173302	SCV002030926	pathogenic	not provided	2023-01-30	criteria provided, single submitter	clinical testing	Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 35303589, 23065789)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001852108	SCV002231634	pathogenic	Hereditary spastic paraplegia 7	2023-09-19	criteria provided, single submitter	clinical testing	Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 193253). Disruption of the initiator codon has been observed in individuals with hereditary spastic paraplegia (PMID: 22964162, 23065789; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the SPG7 mRNA. The next in-frame methionine is located at codon 44.
PreventionGenetics, part of Exact Sciences	RCV003416067	SCV004109759	pathogenic	SPG7-related disorder	2023-07-10	criteria provided, single submitter	clinical testing	The SPG7 c.1A>G variant is predicted to disrupt the translation initiation site (Start loss). This variant has been reported in individuals with hereditary spastic paraplegia (HSP); in at least one patient, the variant was found along with a second SPG7 frameshift variant (Klebe et al. 2012. PubMed ID: 23065789; Panwala et al. 2022. PubMed ID: 35303589). Other variants that disrupt the start codon have also been reported in HSP patients, in the homozygous state or along with a second heterozygous SPG7 variant (c.1A>T in Elleuch et al. 2006. PubMed ID: 16534102; c.1A>T in Klebe et al. 2012. PubMed ID: 23065789; c.3G>A in van Gassen et al. 2012. PubMed ID: 22964162). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000173302	SCV004143547	pathogenic	not provided	2023-10-01	criteria provided, single submitter	clinical testing	SPG7: PVS1, PM2
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV001852108	SCV005044637	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research