ClinVar Miner

Submissions for variant NM_000533.5(PLP1):c.388C>T (p.His130Tyr)

dbSNP: rs878853076
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000223963 SCV000281300 likely pathogenic not provided 2014-11-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001854777 SCV002187497 likely pathogenic Hereditary spastic paraplegia 2 2025-01-13 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 130 of the PLP1 protein (p.His130Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hereditary spastic paraplegia (PMID: 11093273, 34782662; internal data). This variant is also known as H129Y. ClinVar contains an entry for this variant (Variation ID: 235599). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This variant disrupts the p.His130 amino acid residue in PLP1. Other variant(s) that disrupt this residue have been observed in individuals with PLP1-related conditions (internal data), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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