ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.2246C>T (p.Pro749Leu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV002474277 SCV002770742 likely pathogenic not provided 2022-07-20 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Computational tools predict that this variant is damaging.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003491120 SCV004241987 uncertain significance not specified 2023-12-01 criteria provided, single submitter clinical testing Variant summary: SPG7 c.2246C>T (p.Pro749Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251352 control chromosomes. c.2246C>T has been reported in the literature in settings of multi-gene panel testing in multiple compound heterozygous individuals affected with spastic ataxia (e.g. Wan_2021, Bogdanova-Mihaylova_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33774748, 34284285). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005008599 SCV005642530 likely pathogenic Hereditary spastic paraplegia 7 2024-04-03 criteria provided, single submitter clinical testing

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