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NM_005373.3(MPL):c.292C>G (p.Gln98Glu) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 30, 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:
RCV001926978.5

Allele description

NM_005373.3(MPL):c.292C>G (p.Gln98Glu)

Gene:
MPL:MPL proto-oncogene, thrombopoietin receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.2
Genomic location:
Preferred name:
NM_005373.3(MPL):c.292C>G (p.Gln98Glu)
HGVS:
  • NC_000001.11:g.43338621C>G
  • NG_007525.1:g.5818C>G
  • NM_005373.3:c.292C>GMANE SELECT
  • NP_005364.1:p.Gln98Glu
  • LRG_510:g.5818C>G
  • NC_000001.10:g.43804292C>G
Protein change:
Q98E
Links:
dbSNP: rs752682807
NCBI 1000 Genomes Browser:
rs752682807
Molecular consequence:
  • NM_005373.3:c.292C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital amegakaryocytic thrombocytopenia
Identifiers:
MONDO: MONDO:0800451; MedGen: C1327915; Orphanet: 3319; OMIM: PS604498
Name:
Essential thrombocythemia
Synonyms:
essential thrombocytemia; Suspected essential thromboythemia
Identifiers:
MONDO: MONDO:0005029; MeSH: D013920; MedGen: C0040028

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002198326Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 30, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV002198326.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces glutamine with glutamic acid at codon 98 of the MPL protein (p.Gln98Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs752682807, ExAC 0.004%). This variant has not been reported in the literature in individuals affected with MPL-related conditions. 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 tolerated. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 15, 2024