NM_001040716.2(PC):c.2423C>A (p.Pro808His) AND Pyruvate carboxylase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 13, 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:: RCV000816002.5

Allele description [Variation Report for NM_001040716.2(PC):c.2423C>A (p.Pro808His)]

NM_001040716.2(PC):c.2423C>A (p.Pro808His)

Gene:

PC:pyruvate carboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_001040716.2(PC):c.2423C>A (p.Pro808His)

HGVS:

NC_000011.10:g.66850724G>T
NG_008319.1:g.112653C>A
NM_000920.4:c.2423C>A
NM_001040716.2:c.2423C>AMANE SELECT
NM_022172.3:c.2423C>A
NP_000911.2:p.Pro808His
NP_001035806.1:p.Pro808His
NP_071504.2:p.Pro808His
NC_000011.9:g.66618195G>T
NM_000920.3:c.2423C>A

Protein change:

P808H

Links:

dbSNP: rs1591116883

NCBI 1000 Genomes Browser:

rs1591116883

Molecular consequence:

NM_000920.4:c.2423C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001040716.2:c.2423C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022172.3:c.2423C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Pyruvate carboxylase deficiency
Synonyms:: ATAXIA WITH LACTIC ACIDOSIS II; PC deficiency; Ataxia with lactic acidosis 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009949; MedGen: C0034341; Orphanet: 3008; OMIM: 266150

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000956487	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 13, 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

SCV000956487

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 13, 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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000956487.3

#	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 proline with histidine at codon 808 of the PC protein (p.Pro808His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with pyruvate carboxylase deficiency (Invitae). 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: Feb 7, 2023

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