NM_024105.4(ALG12):c.931C>T (p.Arg311Cys) AND ALG12-congenital disorder of glycosylation

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Mar 7, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000660616.8

Allele description [Variation Report for NM_024105.4(ALG12):c.931C>T (p.Arg311Cys)]

NM_024105.4(ALG12):c.931C>T (p.Arg311Cys)

Gene:

ALG12:ALG12 alpha-1,6-mannosyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_024105.4(ALG12):c.931C>T (p.Arg311Cys)

HGVS:

NC_000022.11:g.49907782G>A
NG_008927.1:g.15677C>T
NM_024105.4:c.931C>TMANE SELECT
NP_077010.1:p.Arg311Cys
NC_000022.10:g.50301430G>A
NM_024105.3:c.931C>T

Protein change:

R311C

Links:

dbSNP: rs746215829

NCBI 1000 Genomes Browser:

rs746215829

Molecular consequence:

NM_024105.4:c.931C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: ALG12-congenital disorder of glycosylation (CDG1G)
Synonyms:: CDG Ig; CDG 1G; Congenital disorder of glycosylation, type Ig; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011783; MedGen: C2931001; Orphanet: 79324; OMIM: 607143

Recent activity

Clear Turn Off Turn On

Nucleotide Links for Gene (Select 101927698) (6)
Nucleotide
ie47d06.y1 Melton Normalized Human Islet 4 N4-HIS 1 Homo sapiens cDNA clone IMAG...
ie47d06.y1 Melton Normalized Human Islet 4 N4-HIS 1 Homo sapiens cDNA clone IMAGE:5670178 5', mRNA sequence
gi|15820787|gnl|dbEST|9667090|gb|BI 2.1|

Nucleotide
txid148092[Organism:noexp] (19)
Identical Protein Groups
795842[uid] (1)
Taxonomy
ClinVar for OMIM (Select 176270) (44)
ClinVar

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000782734	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 21, 2017)	paternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000896984	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003444606	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 7, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15639192, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000782734

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 21, 2017)

paternal

clinical testing

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

SCV000896984

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 31, 2018)

unknown

clinical testing

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

SCV003444606

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 7, 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	paternal	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Molecular and clinical description of the first US patients with congenital disorder of glycosylation Ig.

Eklund EA, Newell JW, Sun L, Seo NS, Alper G, Willert J, Freeze HH.

Mol Genet Metab. 2005 Jan;84(1):25-31. Epub 2004 Nov 11.

PubMed [citation]

PMID:: 15639192

See all PubMed Citations (3)

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Mayo Clinic Laboratories, Mayo Clinic, SCV000782734.1

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

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

From Fulgent Genetics, Fulgent Genetics, SCV000896984.1

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

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

From Invitae, SCV003444606.1

#	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 cysteine, which is neutral and slightly polar, at codon 311 of the ALG12 protein (p.Arg311Cys). This variant is present in population databases (rs746215829, gnomAD 0.005%). This missense change has been observed in individual(s) with ALG12-congenital disorder of glycosylation (CDG-Ig) (PMID: 15639192). ClinVar contains an entry for this variant (Variation ID: 377465). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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: Jun 10, 2023

ClinVar

Relating variation to medicine