ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs794726906
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
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)
Invitae RCV001852108 SCV002231634 pathogenic Hereditary spastic paraplegia 7 2023-09-19 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the SPG7 mRNA. The next in-frame methionine is located at codon 44. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with hereditary spastic paraplegia (PMID: 22964162, 23065789; Invitae). ClinVar contains an entry for this variant (Variation ID: 193253). 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.
PreventionGenetics, part of Exact Sciences RCV003416067 SCV004109759 pathogenic SPG7-related condition 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.