NM_002755.4(MAP2K1):c.836T>C (p.Val279Ala) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 7, 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:: RCV003060069.3

Allele description [Variation Report for NM_002755.4(MAP2K1):c.836T>C (p.Val279Ala)]

NM_002755.4(MAP2K1):c.836T>C (p.Val279Ala)

Gene:

MAP2K1:mitogen-activated protein kinase kinase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q22.31

Genomic location:

Preferred name:

NM_002755.4(MAP2K1):c.836T>C (p.Val279Ala)

HGVS:

NC_000015.10:g.66485132T>C
NG_008305.1:g.103260T>C
NM_001411065.1:c.692T>C
NM_002755.4:c.836T>CMANE SELECT
NP_001397994.1:p.Val231Ala
NP_002746.1:p.Val279Ala
NP_002746.1:p.Val279Ala
LRG_725t1:c.836T>C
LRG_725:g.103260T>C
LRG_725p1:p.Val279Ala
NC_000015.9:g.66777470T>C
NM_002755.3:c.836T>C

Protein change:

V231A

Molecular consequence:

NM_001411065.1:c.692T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002755.4:c.836T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

Recent activity

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High-Frequency Jet Ventilation
High-Frequency Jet Ventilation
Respiratory support system used primarily with rates of about 100 to 200/min with volumes of from about one to three times predicted anatomic dead space. Used to treat respira...<br/>Year introduced: 1988

MeSH
Mydriatics [Pharmacological Action]
Mydriatics [Pharmacological Action]

MeSH
Lyb7 B-lymphocyte antigen 7 [Mus musculus]
Lyb7 B-lymphocyte antigen 7 [Mus musculus]
Gene ID:104177

Gene
magnesium-protoporphyrin IX monomethyl ester [oxidative] cyclase, chloroplastic ...
magnesium-protoporphyrin IX monomethyl ester [oxidative] cyclase, chloroplastic [Cucumis melo]
gi|659130568|ref|XP_008465236.1|

Protein
pheneturide [Supplementary Concept]
pheneturide [Supplementary Concept]
product of ring hydrolysis of phenobarbital; structure; RN given refers to parent cpd without isomeric designation<br/>Date introduced: January 1, 1974<br/>

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003439904	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 7, 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

SCV003439904

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 7, 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, SCV003439904.2

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

Description

This variant has not been reported in the literature in individuals affected with MAP2K1-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 alanine, which is neutral and non-polar, at codon 279 of the MAP2K1 protein (p.Val279Ala). 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 not expected to disrupt MAP2K1 protein function. 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: Sep 29, 2024

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