NM_000298.6(PKLR):c.1623G>C (p.Lys541Asn) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 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:: RCV002648204.3

Allele description [Variation Report for NM_000298.6(PKLR):c.1623G>C (p.Lys541Asn)]

NM_000298.6(PKLR):c.1623G>C (p.Lys541Asn)

Gene:

PKLR:pyruvate kinase L/R [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_000298.6(PKLR):c.1623G>C (p.Lys541Asn)

HGVS:

NC_000001.11:g.155290674C>G
NG_011677.1:g.15761G>C
NM_000298.6:c.1623G>CMANE SELECT
NM_181871.4:c.1530G>C
NP_000289.1:p.Lys541Asn
NP_870986.1:p.Lys510Asn
LRG_1136t1:c.1623G>C
LRG_1136:g.15761G>C
LRG_1136p1:p.Lys541Asn
NC_000001.10:g.155260465C>G

Protein change:

K510N

Molecular consequence:

NM_000298.6:c.1623G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181871.4:c.1530G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003523242	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25941984, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523242

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular Analyses of Pyruvate Kinase Deficient Turkish Patients from a Single Center.

Unal S, Gumruk F.

Pediatr Hematol Oncol. 2015;32(5):354-61. doi: 10.3109/08880018.2015.1010671. Epub 2015 May 5.

PubMed [citation]

PMID:: 25941984

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, SCV003523242.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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. 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"). This missense change has been observed in individual(s) with pyruvate kinase deficiency (PMID: 25941984). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 541 of the PKLR protein (p.Lys541Asn).

#	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: Sep 29, 2024

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