NM_005271.5(GLUD1):c.53C>T (p.Ala18Val) AND Hyperinsulinism-hyperammonemia syndrome

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

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 10, 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:: RCV003082256.5

Allele description

NM_005271.5(GLUD1):c.53C>T (p.Ala18Val)

Genes:

LOC130004255:ATAC-STARR-seq lymphoblastoid silent region 2577 [Gene]
GLUD1:glutamate dehydrogenase 1 [Gene - OMIM - HGNC]
SHLD2:shieldin complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.2

Genomic location:

Preferred name:

NM_005271.5(GLUD1):c.53C>T (p.Ala18Val)

HGVS:

NC_000010.11:g.87094717G>A
NG_013010.1:g.5303C>T
NM_001318904.2:c.-676C>T
NM_001318905.2:c.-802C>T
NM_001318906.2:c.-509C>T
NM_005271.3:c.53C>T
NM_005271.5:c.53C>TMANE SELECT
NP_005262.1:p.Ala18Val
NC_000010.10:g.88854474G>A

Protein change:

A18V

Molecular consequence:

NM_001318904.2:c.-676C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001318905.2:c.-802C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001318906.2:c.-509C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_005271.5:c.53C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hyperinsulinism-hyperammonemia syndrome (HHF6)
Synonyms:: HA/HI syndrome; Hyperinsulinemic hypoglycemia familial 6
Identifiers:: MONDO: MONDO:0011717; MedGen: C1847555; Orphanet: 35878; OMIM: 606762

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LOC130004255 [Homo sapiens]
LOC130004255 [Homo sapiens]
Gene ID:130004255

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003478864	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 10, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003816914	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 25, 2019)	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

SCV003478864

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 10, 2022)

germline

clinical testing

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

SCV003816914

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 25, 2019)

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

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

Details of each submission

From Invitae, SCV003478864.2

#	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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 18 of the GLUD1 protein (p.Ala18Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GLUD1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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

From Revvity Omics, Revvity, SCV003816914.2

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 16, 2024

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