ClinVar Miner

Submissions for variant NM_001371279.1(REEP1):c.2T>C (p.Met1Thr)

dbSNP: rs1681107508
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001210927 SCV001382443 pathogenic Hereditary spastic paraplegia 31 2023-08-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the REEP1 protein in which other variant(s) (p.Ala20Glu) have been determined to be pathogenic (PMID: 16826527, 18321925, 20718791, 22703882, 23812641, 24478229, 26201691). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 941193). Disruption of the initiator codon has been observed in individuals with hereditary spastic paraplegia (PMID: 23108492, 32501971). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the REEP1 mRNA. The next in-frame methionine is located at codon 39.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268396 SCV001447294 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV004671256 SCV005156788 pathogenic Inborn genetic diseases 2024-05-06 criteria provided, single submitter clinical testing The c.2T>C (p.M1?) alteration is located in coding exon 1 of the REEP1 gene and results from a T to C substitution at nucleotide position 2. This alters the methionine residue at the initiation codon (ATG). Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Another initiation codon alteration, c.2T>G (p.M1?), has also been reported in an individual with features consistent with REEP1-related spastic paraplegia (Cui, 2020). This amino acid position is highly conserved in available vertebrate species. Based on the available evidence, this alteration is classified as pathogenic.

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