NM_001754.5(RUNX1):c.107C>G (p.Thr36Arg) AND Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 22, 2020
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:: RCV001299153.6

Allele description

NM_001754.5(RUNX1):c.107C>G (p.Thr36Arg)

Gene:

RUNX1:RUNX family transcription factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.12

Genomic location:

Preferred name:

NM_001754.5(RUNX1):c.107C>G (p.Thr36Arg)

HGVS:

NC_000021.9:g.34887087G>C
NG_011402.2:g.1102625C>G
NM_001001890.3:c.26C>G
NM_001122607.2:c.26C>G
NM_001754.5:c.107C>GMANE SELECT
NP_001001890.1:p.Thr9Arg
NP_001116079.1:p.Thr9Arg
NP_001745.2:p.Thr36Arg
LRG_482:g.1102625C>G
NC_000021.8:g.36259384G>C

Protein change:

T36R

Links:

dbSNP: rs2058005989

NCBI 1000 Genomes Browser:

rs2058005989

Molecular consequence:

NM_001001890.3:c.26C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001122607.2:c.26C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001754.5:c.107C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Synonyms:: Platelet disorder, Aspirin-like; Familial platelet disorder with associated myeloid malignancy; Familial Platelet Disorder with Propensity to Acute Myelogenous Leukemia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100083; MeSH: C563324; MedGen: C1832388; Orphanet: 71290; OMIM: 601399

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001488232	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 22, 2020)	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

SCV001488232

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 22, 2020)

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 Invitae, SCV001488232.4

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

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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RUNX1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with arginine at codon 36 of the RUNX1 protein (p.Thr36Arg). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and arginine.

#	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 28, 2024

ClinVar

Relating variation to medicine