NM_000533.5(PLP1):c.517C>T (p.Pro173Ser) AND Pelizaeus-Merzbacher disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 15, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004595783.1

Allele description [Variation Report for NM_000533.5(PLP1):c.517C>T (p.Pro173Ser)]

NM_000533.5(PLP1):c.517C>T (p.Pro173Ser)

Genes:

RAB9B:RAB9B, member RAS oncogene family [Gene - OMIM - HGNC]
PLP1:proteolipid protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.2

Genomic location:

Preferred name:

NM_000533.5(PLP1):c.517C>T (p.Pro173Ser)

HGVS:

NC_000023.11:g.103787861C>T
NG_008863.2:g.16351C>T
NG_016452.2:g.49422G>A
NM_000533.5:c.517C>TMANE SELECT
NM_001128834.3:c.517C>T
NM_001305004.1:c.352C>T
NM_199478.3:c.412C>T
NP_000524.3:p.Pro173Ser
NP_001122306.1:p.Pro173Ser
NP_001291933.1:p.Pro118Ser
NP_955772.1:p.Pro138Ser
NC_000023.10:g.103042790C>T

Protein change:

P118S

Molecular consequence:

NM_000533.5:c.517C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128834.3:c.517C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001305004.1:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_199478.3:c.412C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Pelizaeus-Merzbacher disease
Synonyms:: LEUKODYSTROPHY, HYPOMYELINATING, 1; Pelizaeus Merzbacher brain sclerosis; Sudanophilic leukodystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010714; MedGen: C0205711; Orphanet: 702; OMIM: 312080; Human Phenotype Ontology: HP:0003269

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005088476	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 15, 2021)	maternal, unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15712223, 25491635, 19024090, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005088476

Molecular Diagnostics Lab, Nemours Children's Health, Delaware

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 15, 2021)

maternal, unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	maternal	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	unknown	no	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Seventeen novel PLP1 mutations in patients with Pelizaeus-Merzbacher disease.

Hübner CA, Orth U, Senning A, Steglich C, Kohlschütter A, Korinthenberg R, Gal A.

Hum Mutat. 2005 Mar;25(3):321-2.

PubMed [citation]

PMID:: 15712223

Identification and functional study of novel PLP1 mutations in Chinese patients with Pelizaeus-Merzbacher disease.

Xie H, Feng H, Ji J, Wu Y, Kou L, Li D, Ji H, Wu X, Niu Z, Wang J, Jiang Y.

Brain Dev. 2015 Sep;37(8):797-802. doi: 10.1016/j.braindev.2014.11.007. Epub 2014 Dec 6.

PubMed [citation]

PMID:: 25491635

See all PubMed Citations (4)

Details of each submission

From Molecular Diagnostics Lab, Nemours Children's Health, Delaware, SCV005088476.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing (GTR000028364.3)	PubMed (4)
2	not provided	1	not provided	not provided	clinical testing (GTR000028364.3)	PubMed (4)

Description

This missense variant (c.517C>T, p.Pro173Ser) has not been observed in population databases (gnomAD). It has been described in the literature (PMID 157122223, PMID 25491635, PMID 19024090). Variant prediction programs support a deleterious effect on the protein, although no functional studies have been published.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	1	blood	not provided	(GTR000028364.3)	1	not provided	not provided	not provided
2	unknown	no	1	blood	not provided	(GTR000028364.3)	1	not provided	not provided	not provided

Last Updated: Jul 29, 2024

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