ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.1904C>T (p.Ser635Leu)

dbSNP: rs864622507
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206309 SCV000260894 likely pathogenic Hereditary spastic paraplegia 7 2021-08-13 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000206309 SCV000597236 likely pathogenic Hereditary spastic paraplegia 7 2015-10-07 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000993072 SCV001145784 uncertain significance not provided 2019-05-22 criteria provided, single submitter clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center RCV000993072 SCV001755412 uncertain significance not provided 2021-07-10 criteria provided, single submitter clinical testing
GeneDx RCV000993072 SCV001992470 uncertain significance not provided 2019-10-03 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29915382, 16534102, 28294470, 30533525)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000206309 SCV002051454 pathogenic Hereditary spastic paraplegia 7 2021-12-03 criteria provided, single submitter clinical testing Variant summary: SPG7 c.1904C>T (p.Ser635Leu) results in a non-conservative amino acid change located in the Peptidase M41 domain (IPR000642) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245664 control chromosomes (gnomAD). c.1904C>T has been reported in the literature in multiple compound heterozygous and homozygous individuals affected with Hereditary Spastic Paraplegia and cerebellar ataxia (e.g. Elleuch_2006, Hewamadduma_2018, Sun_2019, Mao_2020) and was shown to segregate with disease in at least one family (Mao_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance and one ClinVar submitter (evaluation after 2014) cites it as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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