ClinVar Miner

Submissions for variant NM_001371279.1(REEP1):c.55C>A (p.Pro19Thr)

dbSNP: rs2468983254
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV003391646 SCV004110963 uncertain significance REEP1-related disorder 2023-04-07 criteria provided, single submitter clinical testing The REEP1 c.55C>A variant is predicted to result in the amino acid substitution p.Pro19Thr. This variant was reported in an individual with childhood onset hereditary spastic paraplegia (Giordani et al. 2021. PubMed ID: 34782662). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
3billion RCV005254785 SCV005904690 likely pathogenic Hereditary spastic paraplegia 31 2024-03-04 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: The majority of the known disease-causing variants of this gene are variants expected to result in premature termination of the protein. In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.98 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.84 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported to be associated with REEP1 related disorder (PMID: 34782662). However, the evidence of pathogenicity is insufficient at this time. Different missense changes at the same codon (p.Pro19Arg, p.Pro19Leu) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000411807, VCV000989221 /PMID: 18321925, 21618648). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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