NM_004448.4(ERBB2):c.3689G>T (p.Arg1230Leu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 10, 2024
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:: RCV001854612.7

Allele description [Variation Report for NM_004448.4(ERBB2):c.3689G>T (p.Arg1230Leu)]

NM_004448.4(ERBB2):c.3689G>T (p.Arg1230Leu)

Gene:

ERBB2:erb-b2 receptor tyrosine kinase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_004448.4(ERBB2):c.3689G>T (p.Arg1230Leu)

HGVS:

NC_000017.11:g.39727965G>T
NG_007503.1:g.44826G>T
NM_001005862.3:c.3599G>T
NM_001289936.2:c.3644G>T
NM_001289937.2:c.*268G>T
NM_001382782.1:c.3599G>T
NM_001382783.1:c.3599G>T
NM_001382784.1:c.3806G>T
NM_001382785.1:c.3791G>T
NM_001382786.1:c.3770G>T
NM_001382787.1:c.3764G>T
NM_001382788.1:c.3719G>T
NM_001382789.1:c.3710G>T
NM_001382790.1:c.3686G>T
NM_001382791.1:c.3680G>T
NM_001382792.1:c.3653G>T
NM_001382793.1:c.3647G>T
NM_001382794.1:c.3647G>T
NM_001382795.1:c.3641G>T
NM_001382796.1:c.3602G>T
NM_001382797.1:c.3590G>T
NM_001382798.1:c.3533G>T
NM_001382799.1:c.3509G>T
NM_001382800.1:c.3503G>T
NM_001382801.1:c.3485G>T
NM_001382802.1:c.3431G>T
NM_001382803.1:c.*268G>T
NM_001382804.1:c.2861G>T
NM_001382805.1:c.2738G>T
NM_001382806.1:c.2651G>T
NM_004448.4:c.3689G>TMANE SELECT
NP_001005862.1:p.Arg1200Leu
NP_001276865.1:p.Arg1215Leu
NP_001369711.1:p.Arg1200Leu
NP_001369712.1:p.Arg1200Leu
NP_001369713.1:p.Arg1269Leu
NP_001369714.1:p.Arg1264Leu
NP_001369715.1:p.Arg1257Leu
NP_001369716.1:p.Arg1255Leu
NP_001369717.1:p.Arg1240Leu
NP_001369718.1:p.Arg1237Leu
NP_001369719.1:p.Arg1229Leu
NP_001369720.1:p.Arg1227Leu
NP_001369721.1:p.Arg1218Leu
NP_001369722.1:p.Arg1216Leu
NP_001369723.1:p.Arg1216Leu
NP_001369724.1:p.Arg1214Leu
NP_001369725.1:p.Arg1201Leu
NP_001369726.1:p.Arg1197Leu
NP_001369727.1:p.Arg1178Leu
NP_001369728.1:p.Arg1170Leu
NP_001369729.1:p.Arg1168Leu
NP_001369730.1:p.Arg1162Leu
NP_001369731.1:p.Arg1144Leu
NP_001369733.1:p.Arg954Leu
NP_001369734.1:p.Arg913Leu
NP_001369735.1:p.Arg884Leu
NP_004439.2:p.Arg1230Leu
LRG_724:g.44826G>T
NC_000017.10:g.37884218G>T
NR_110535.2:n.3927G>T

Protein change:

R1144L

Links:

dbSNP: rs372043866

NCBI 1000 Genomes Browser:

rs372043866

Molecular consequence:

NM_001289937.2:c.*268G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001382803.1:c.*268G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001005862.3:c.3599G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001289936.2:c.3644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382782.1:c.3599G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382783.1:c.3599G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382784.1:c.3806G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382785.1:c.3791G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382786.1:c.3770G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382787.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382788.1:c.3719G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382789.1:c.3710G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382790.1:c.3686G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382791.1:c.3680G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382792.1:c.3653G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382793.1:c.3647G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382794.1:c.3647G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382795.1:c.3641G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382796.1:c.3602G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382797.1:c.3590G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382798.1:c.3533G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382799.1:c.3509G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382800.1:c.3503G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382801.1:c.3485G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382802.1:c.3431G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382804.1:c.2861G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382805.1:c.2738G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382806.1:c.2651G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004448.4:c.3689G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110535.2:n.3927G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV002262009	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 10, 2024)	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

SCV002262009

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 10, 2024)

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, SCV002262009.3

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

Description

This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1230 of the ERBB2 protein (p.Arg1230Leu). This variant is present in population databases (rs372043866, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ERBB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 134086). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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.

#	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

ClinVar

Relating variation to medicine