NM_005566.4(LDHA):c.340G>A (p.Val114Met) AND Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 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:: RCV002715857.3

Allele description [Variation Report for NM_005566.4(LDHA):c.340G>A (p.Val114Met)]

NM_005566.4(LDHA):c.340G>A (p.Val114Met)

Gene:

LDHA:lactate dehydrogenase A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_005566.4(LDHA):c.340G>A (p.Val114Met)

HGVS:

NC_000011.10:g.18400932G>A
NG_008185.1:g.11498G>A
NM_001135239.2:c.244+1384G>A
NM_001165414.2:c.427G>A
NM_001165415.2:c.340G>A
NM_001165416.2:c.340G>A
NM_005566.4:c.340G>AMANE SELECT
NP_001158886.1:p.Val143Met
NP_001158887.1:p.Val114Met
NP_001158888.1:p.Val114Met
NP_005557.1:p.Val114Met
NC_000011.9:g.18422479G>A
NR_028500.2:n.320G>A

Protein change:

V114M

Molecular consequence:

NM_001135239.2:c.244+1384G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001165414.2:c.427G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165415.2:c.340G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165416.2:c.340G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005566.4:c.340G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_028500.2:n.320G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency
Synonyms:: GSD XI; LACTATE DEHYDROGENASE A DEFICIENCY; Glycogen storage disease XI
Identifiers:: MONDO: MONDO:0013047; MedGen: C2931743; Orphanet: 284426; OMIM: 612933

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003000332	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 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

SCV003000332

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003000332.2

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

Description

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 expected to disrupt LDHA protein function. This variant has not been reported in the literature in individuals affected with LDHA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 114 of the LDHA protein (p.Val114Met).

#	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: Oct 8, 2024

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