Submissions for variant NM_000533.5(PLP1):c.548C>A (p.Thr183Asn)

dbSNP: rs2147766068

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001916524	SCV002182377	uncertain significance	Hereditary spastic paraplegia 2	2021-08-02	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with sporadic Pelizaeus-Merzbacher disease (PMID: 10417279). 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with asparagine at codon 183 of the PLP1 protein (p.Thr183Asn). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and asparagine.
Center for Personalized Medicine, Children's Hospital Los Angeles	RCV003156144	SCV003845287	likely pathogenic	See cases	2022-12-21	criteria provided, single submitter	clinical testing