NM_133642.5(LARGE1):c.2219G>A (p.Arg740His) AND Muscular dystrophy-dystroglycanopathy type B6

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 23, 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:: RCV003107176.3

Allele description

NM_133642.5(LARGE1):c.2219G>A (p.Arg740His)

Gene:

LARGE1:LARGE xylosyl- and glucuronyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.3

Genomic location:

Preferred name:

NM_133642.5(LARGE1):c.2219G>A (p.Arg740His)

HGVS:

NC_000022.11:g.33274479C>T
NG_009929.2:g.650950G>A
NM_001362949.2:c.2219G>A
NM_001362951.2:c.2219G>A
NM_001362953.2:c.2219G>A
NM_001378624.1:c.2219G>A
NM_001378625.1:c.2219G>A
NM_001378626.1:c.2219G>A
NM_001378627.1:c.2072G>A
NM_001378628.1:c.2072G>A
NM_001378629.1:c.2063G>A
NM_001378630.1:c.1616G>A
NM_001378631.1:c.1313G>A
NM_004737.7:c.2219G>A
NM_133642.5:c.2219G>AMANE SELECT
NP_001349878.1:p.Arg740His
NP_001349880.1:p.Arg740His
NP_001349882.1:p.Arg740His
NP_001365553.1:p.Arg740His
NP_001365554.1:p.Arg740His
NP_001365555.1:p.Arg740His
NP_001365556.1:p.Arg691His
NP_001365557.1:p.Arg691His
NP_001365558.1:p.Arg688His
NP_001365559.1:p.Arg539His
NP_001365560.1:p.Arg438His
NP_004728.1:p.Arg740His
NP_598397.1:p.Arg740His
LRG_856t1:c.2219G>A
LRG_856t2:c.2219G>A
LRG_856:g.650950G>A
LRG_856p1:p.Arg740His
LRG_856p2:p.Arg740His
NC_000022.10:g.33670465C>T

Protein change:

R438H

Molecular consequence:

NM_001362949.2:c.2219G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362951.2:c.2219G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362953.2:c.2219G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378624.1:c.2219G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378625.1:c.2219G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378626.1:c.2219G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378627.1:c.2072G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378628.1:c.2072G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378629.1:c.2063G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378630.1:c.1616G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378631.1:c.1313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004737.7:c.2219G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133642.5:c.2219G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Muscular dystrophy-dystroglycanopathy type B6 (MDDGB6)
Synonyms:: MUSCULAR DYSTROPHY, CONGENITAL, LARGE-RELATED; MUSCULAR DYSTROPHY, CONGENITAL, TYPE 1D; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 6
Identifiers:: MONDO: MONDO:0012138; MedGen: C1837229; OMIM: 608840

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003782755	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 23, 2021)	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

SCV003782755

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 23, 2021)

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 Invitae, SCV003782755.2

#	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 histidine, which is basic and polar, at codon 740 of the LARGE1 protein (p.Arg740His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LARGE1-related conditions. 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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: Nov 11, 2023

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