NM_005373.3(MPL):c.340G>A (p.Val114Met) AND not specified

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Dec 28, 2023
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:: RCV000121540.8

Allele description [Variation Report for NM_005373.3(MPL):c.340G>A (p.Val114Met)]

NM_005373.3(MPL):c.340G>A (p.Val114Met)

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.340G>A (p.Val114Met)

HGVS:

NC_000001.11:g.43338669G>A
NG_007525.1:g.5866G>A
NM_005373.3:c.340G>AMANE SELECT
NP_005364.1:p.Val114Met
NP_005364.1:p.Val114Met
LRG_510t1:c.340G>A
LRG_510:g.5866G>A
LRG_510p1:p.Val114Met
NC_000001.10:g.43804340G>A
NM_005373.2:c.340G>A
P40238:p.Val114Met

Protein change:

V114M

Links:

UniProtKB: P40238#VAR_049174; dbSNP: rs12731981

NCBI 1000 Genomes Browser:

rs12731981

Molecular consequence:

NM_005373.3:c.340G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000085734	ITMI	no classification provided	not provided	germline	reference population	PubMed (1) [See all records that cite this PMID]
SCV000311029	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004847405	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Benign (Dec 28, 2023)	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

SCV000085734

ITMI

no classification provided

not provided

germline

reference population

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

SCV000311029

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign

germline

clinical testing

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

SCV004847405

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Benign
(Dec 28, 2023)

germline

clinical testing

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

Description

Please see associated publication for description of ethnicities: SCV000085734

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
African	germline	unknown	not provided	not provided	not provided	43	not provided	reference population
African_European	germline	unknown	not provided	not provided	not provided	46	not provided	reference population
Central_Asian	germline	unknown	not provided	not provided	not provided	50	not provided	reference population
East_Asian	germline	unknown	not provided	not provided	not provided	62	not provided	reference population
European	germline	unknown	not provided	not provided	not provided	331	not provided	reference population
Hispanic	germline	unknown	not provided	not provided	not provided	118	not provided	reference population
Whole_cohort	germline	unknown	not provided	not provided	not provided	681	not provided	reference population

Citations

PubMed

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]

PMID:: 24728327
PMCID:: PMC3984285

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 ITMI, SCV000085734.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	African	not provided	not provided	not provided	reference population	PubMed (1)
2	African_European	not provided	not provided	not provided	reference population	PubMed (1)
3	Central_Asian	not provided	not provided	not provided	reference population	PubMed (1)
4	East_Asian	not provided	not provided	not provided	reference population	PubMed (1)
5	European	not provided	not provided	not provided	reference population	PubMed (1)
6	Hispanic	not provided	not provided	not provided	reference population	PubMed (1)
7	Whole_cohort	not provided	not provided	not provided	reference population	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	43	not provided	discovery		not provided	0	not provided	not provided
2	germline	unknown	46	not provided	discovery		not provided	0.0217	not provided	not provided
3	germline	unknown	50	not provided	discovery		not provided	0.02	not provided	not provided
4	germline	unknown	62	not provided	discovery		not provided	0	not provided	not provided
5	germline	unknown	331	not provided	discovery		not provided	0.0151	not provided	not provided
6	germline	unknown	118	not provided	discovery		not provided	0.0127	not provided	not provided
7	germline	unknown	681	not provided	discovery		not provided	0.014	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000311029.1

#	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

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847405.1

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

Description

The p.Val114Met variant in MPL is classified as likely benign because it has been identified in 3.3% (2251/68026) of European chromosomes including 48 homozygotes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). In addition, computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1, BP4.

#	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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