NM_201384.3(PLEC):c.13385G>A (p.Arg4462Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 2023
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:: RCV001050067.5

Allele description [Variation Report for NM_201384.3(PLEC):c.13385G>A (p.Arg4462Gln)]

NM_201384.3(PLEC):c.13385G>A (p.Arg4462Gln)

Gene:

PLEC:plectin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.3

Genomic location:

Preferred name:

NM_201384.3(PLEC):c.13385G>A (p.Arg4462Gln)

HGVS:

NC_000008.11:g.143916436C>T
NG_012492.1:g.65310G>A
NM_000445.5:c.13466G>A
NM_201378.4:c.13343G>A
NM_201379.3:c.13319G>A
NM_201380.4:c.13796G>A
NM_201381.3:c.13289G>A
NM_201382.4:c.13385G>A
NM_201383.3:c.13397G>A
NM_201384.3:c.13385G>AMANE SELECT
NP_000436.2:p.Arg4489Gln
NP_958780.1:p.Arg4448Gln
NP_958781.1:p.Arg4440Gln
NP_958782.1:p.Arg4599Gln
NP_958783.1:p.Arg4430Gln
NP_958784.1:p.Arg4462Gln
NP_958785.1:p.Arg4466Gln
NP_958786.1:p.Arg4462Gln
NC_000008.10:g.144990604C>T
NM_000445.4:c.13466G>A

Protein change:

R4430Q

Links:

dbSNP: rs782440209

NCBI 1000 Genomes Browser:

rs782440209

Molecular consequence:

NM_000445.5:c.13466G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201378.4:c.13343G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201379.3:c.13319G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201380.4:c.13796G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201381.3:c.13289G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201382.4:c.13385G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201383.3:c.13397G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201384.3:c.13385G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Epidermolysis bullosa simplex 5B, with muscular dystrophy (EBS5B)
Synonyms:: EPIDERMOLYSIS BULLOSA SIMPLEX AND LIMB-GIRDLE MUSCULAR DYSTROPHY; Epidermolysa bullosa simplex and limb girdle muscular dystrophy; Epidermolysis bullosa simplex with muscular dystrophy
Identifiers:: MONDO: MONDO:0009181; MedGen: C2931072; Orphanet: 257; OMIM: 226670

Name:: Epidermolysis bullosa simplex, Ogna type (EBS5A)
Synonyms:: EPIDERMOLYSIS BULLOSA SIMPLEX 5A, OGNA TYPE; Pidermolysis bullosa simplex 5A, Ogna type
Identifiers:: MONDO: MONDO:0007555; MedGen: C0432317; Orphanet: 79401; OMIM: 131950

Name:: Epidermolysis bullosa simplex 5C, with pyloric atresia (EBS5C)
Synonyms:: Epidermolysis bullosa simplex with pyloric atresia; PLEC1-Related Epidermolysis Bullosa with Pyloric Atresia
Identifiers:: MONDO: MONDO:0012807; MedGen: C2677349; Orphanet: 158684; OMIM: 612138

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2Q (LGMDR17)
Synonyms:: Limb-girdle muscular dystrophy, type 2Q; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 17
Identifiers:: MONDO: MONDO:0013390; MedGen: C3150989; Orphanet: 254361; OMIM: 613723

Name:: Epidermolysis bullosa simplex with nail dystrophy (EBS5D)
Identifiers:: MONDO: MONDO:0014661; MedGen: C4225309; OMIM: 616487

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yj66f06.s1 Soares breast 2NbHBst Homo sapiens cDNA clone IMAGE:153731 3', mRNA sequence
gi|809972|gnl|dbEST|218011|gb|R4794

Nucleotide
fructosamine kinase family protein [Vibrio sp. ED004]
fructosamine kinase family protein [Vibrio sp. ED004]
gi|2232668601|gnl|PRJNA669220|ITG10 0|gb|UPR56683.1|

Protein
ETNK1 [Gracilinanus agilis]
ETNK1 [Gracilinanus agilis]
Gene ID:123250680

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001214155	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001214155

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001214155.5

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 4489 of the PLEC protein (p.Arg4489Gln). 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. 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 PLEC protein function. ClinVar contains an entry for this variant (Variation ID: 846699). This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database.

#	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: Sep 29, 2024

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