NM_181882.3(PRX):c.3209G>A (p.Arg1070Gln) AND Charcot-Marie-Tooth disease type 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 17, 2022
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:: RCV000475571.12

Allele description [Variation Report for NM_181882.3(PRX):c.3209G>A (p.Arg1070Gln)]

NM_181882.3(PRX):c.3209G>A (p.Arg1070Gln)

Gene:

PRX:periaxin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_181882.3(PRX):c.3209G>A (p.Arg1070Gln)

HGVS:

NC_000019.10:g.40395143C>T
NG_007979.1:g.23222G>A
NG_051224.1:g.79G>A
NM_020956.2:c.*3414G>A
NM_181882.3:c.3209G>AMANE SELECT
NP_870998.2:p.Arg1070Gln
NP_870998.2:p.Arg1070Gln
LRG_265t1:c.*3414G>A
LRG_265t2:c.3209G>A
LRG_265:g.23222G>A
LRG_265p2:p.Arg1070Gln
NC_000019.9:g.40901050C>T
NM_181882.2:c.3209G>A

Protein change:

R1070Q

Links:

dbSNP: rs146222815

NCBI 1000 Genomes Browser:

rs146222815

Molecular consequence:

NM_020956.2:c.*3414G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_181882.3:c.3209G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 4
Synonyms:: Charcot-Marie-Tooth, Type 4
Identifiers:: MONDO: MONDO:0018995; MedGen: C4082197

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000551428	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26392352, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000551428

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 17, 2022)

germline

clinical testing

PubMed (2)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability.

Antoniadi T, Buxton C, Dennis G, Forrester N, Smith D, Lunt P, Burton-Jones S.

BMC Med Genet. 2015 Sep 21;16:84. doi: 10.1186/s12881-015-0224-8.

PubMed [citation]

PMID:: 26392352
PMCID:: PMC4578331

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000551428.9

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1070 of the PRX protein (p.Arg1070Gln). This variant is present in population databases (rs146222815, gnomAD 0.05%). This missense change has been observed in individual(s) with hereditary motor neuropathy (PMID: 26392352). ClinVar contains an entry for this variant (Variation ID: 329260). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRX protein function. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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