ClinVar Miner

Submissions for variant NM_000533.5(PLP1):c.409C>T (p.Arg137Trp)

dbSNP: rs132630295
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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 RCV000011847 SCV000820486 uncertain significance Hereditary spastic paraplegia 2 2018-06-13 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. The observation of one or more missense substitutions at this codon (p,Arg137Gly) in affected individuals suggests that this may be a clinically significant residue (PMID: 24139698). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in an individual affected with complicated spastic paraplegia and in an individual affected with Pelizaeus-Merzbacher disease (PMID: 17438221, 24139698). ClinVar contains an entry for this variant (Variation ID: 11098). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 137 of the PLP1 protein (p.Arg137Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan.
Molecular Diagnostics Lab, Nemours Children's Health, Delaware RCV004595485 SCV005088453 likely pathogenic Pelizaeus-Merzbacher disease 2021-11-22 criteria provided, single submitter clinical testing This missense variant (c.409G>T, p.Arg137Trp) has not been observed in population databases (gnomAD). It has been described in the literature (PMID 17438221, PMID 24139698). This nucleotide resides in a region involved in splice site regulation (PMID 16288477), and variant prediction programs suggest a deleterious effect on the PLP1 protein, although no functional studies have been published. It has been found in 2 affected males in a family, related through maternal lines.
OMIM RCV000011847 SCV000032080 pathogenic Hereditary spastic paraplegia 2 2007-04-17 no assertion criteria provided literature only

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