NM_133642.5(LARGE1):c.1903G>A (p.Ala635Thr) AND Muscular dystrophy-dystroglycanopathy type B6

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 24, 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:: RCV001303884.5

Allele description [Variation Report for NM_133642.5(LARGE1):c.1903G>A (p.Ala635Thr)]

NM_133642.5(LARGE1):c.1903G>A (p.Ala635Thr)

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.1903G>A (p.Ala635Thr)

HGVS:

NC_000022.11:g.33277230C>T
NG_009929.2:g.648199G>A
NM_001362949.2:c.1903G>A
NM_001362951.2:c.1903G>A
NM_001362953.2:c.1903G>A
NM_001378624.1:c.1903G>A
NM_001378625.1:c.1903G>A
NM_001378626.1:c.1903G>A
NM_001378627.1:c.1756G>A
NM_001378628.1:c.1756G>A
NM_001378629.1:c.1747G>A
NM_001378630.1:c.1300G>A
NM_001378631.1:c.997G>A
NM_004737.7:c.1903G>A
NM_133642.5:c.1903G>AMANE SELECT
NP_001349878.1:p.Ala635Thr
NP_001349880.1:p.Ala635Thr
NP_001349882.1:p.Ala635Thr
NP_001365553.1:p.Ala635Thr
NP_001365554.1:p.Ala635Thr
NP_001365555.1:p.Ala635Thr
NP_001365556.1:p.Ala586Thr
NP_001365557.1:p.Ala586Thr
NP_001365558.1:p.Ala583Thr
NP_001365559.1:p.Ala434Thr
NP_001365560.1:p.Ala333Thr
NP_004728.1:p.Ala635Thr
NP_598397.1:p.Ala635Thr
LRG_856t1:c.1903G>A
LRG_856t2:c.1903G>A
LRG_856:g.648199G>A
LRG_856p1:p.Ala635Thr
LRG_856p2:p.Ala635Thr
NC_000022.10:g.33673216C>T
NM_004737.4:c.1903G>A

Protein change:

A333T

Links:

dbSNP: rs150325234

NCBI 1000 Genomes Browser:

rs150325234

Molecular consequence:

NM_001362949.2:c.1903G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362951.2:c.1903G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362953.2:c.1903G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378624.1:c.1903G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378625.1:c.1903G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378626.1:c.1903G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378627.1:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378628.1:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378629.1:c.1747G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378630.1:c.1300G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378631.1:c.997G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004737.7:c.1903G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133642.5:c.1903G>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
SCV001493147	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 24, 2022)	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

SCV001493147

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 24, 2022)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001493147.3

#	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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 635 of the LARGE1 protein (p.Ala635Thr). This variant is present in population databases (rs150325234, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with LARGE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1006789). 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: "Tolerated"; 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: Aug 5, 2023

ClinVar

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