NM_004448.4(ERBB2):c.3688C>T (p.Arg1230Trp) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 15, 2023
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:: RCV001936101.6

Allele description [Variation Report for NM_004448.4(ERBB2):c.3688C>T (p.Arg1230Trp)]

NM_004448.4(ERBB2):c.3688C>T (p.Arg1230Trp)

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.3688C>T (p.Arg1230Trp)

HGVS:

NC_000017.11:g.39727964C>T
NG_007503.1:g.44825C>T
NM_001005862.3:c.3598C>T
NM_001289936.2:c.3643C>T
NM_001289937.2:c.*267C>T
NM_001382782.1:c.3598C>T
NM_001382783.1:c.3598C>T
NM_001382784.1:c.3805C>T
NM_001382785.1:c.3790C>T
NM_001382786.1:c.3769C>T
NM_001382787.1:c.3763C>T
NM_001382788.1:c.3718C>T
NM_001382789.1:c.3709C>T
NM_001382790.1:c.3685C>T
NM_001382791.1:c.3679C>T
NM_001382792.1:c.3652C>T
NM_001382793.1:c.3646C>T
NM_001382794.1:c.3646C>T
NM_001382795.1:c.3640C>T
NM_001382796.1:c.3601C>T
NM_001382797.1:c.3589C>T
NM_001382798.1:c.3532C>T
NM_001382799.1:c.3508C>T
NM_001382800.1:c.3502C>T
NM_001382801.1:c.3484C>T
NM_001382802.1:c.3430C>T
NM_001382803.1:c.*267C>T
NM_001382804.1:c.2860C>T
NM_001382805.1:c.2737C>T
NM_001382806.1:c.2650C>T
NM_004448.4:c.3688C>TMANE SELECT
NP_001005862.1:p.Arg1200Trp
NP_001276865.1:p.Arg1215Trp
NP_001369711.1:p.Arg1200Trp
NP_001369712.1:p.Arg1200Trp
NP_001369713.1:p.Arg1269Trp
NP_001369714.1:p.Arg1264Trp
NP_001369715.1:p.Arg1257Trp
NP_001369716.1:p.Arg1255Trp
NP_001369717.1:p.Arg1240Trp
NP_001369718.1:p.Arg1237Trp
NP_001369719.1:p.Arg1229Trp
NP_001369720.1:p.Arg1227Trp
NP_001369721.1:p.Arg1218Trp
NP_001369722.1:p.Arg1216Trp
NP_001369723.1:p.Arg1216Trp
NP_001369724.1:p.Arg1214Trp
NP_001369725.1:p.Arg1201Trp
NP_001369726.1:p.Arg1197Trp
NP_001369727.1:p.Arg1178Trp
NP_001369728.1:p.Arg1170Trp
NP_001369729.1:p.Arg1168Trp
NP_001369730.1:p.Arg1162Trp
NP_001369731.1:p.Arg1144Trp
NP_001369733.1:p.Arg954Trp
NP_001369734.1:p.Arg913Trp
NP_001369735.1:p.Arg884Trp
NP_004439.2:p.Arg1230Trp
LRG_724:g.44825C>T
NC_000017.10:g.37884217C>T
NR_110535.2:n.3926C>T

Protein change:

R1144W

Links:

dbSNP: rs769940977

NCBI 1000 Genomes Browser:

rs769940977

Molecular consequence:

NM_001289937.2:c.*267C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001382803.1:c.*267C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001005862.3:c.3598C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001289936.2:c.3643C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382782.1:c.3598C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382783.1:c.3598C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382784.1:c.3805C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382785.1:c.3790C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382786.1:c.3769C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382787.1:c.3763C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382788.1:c.3718C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382789.1:c.3709C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382790.1:c.3685C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382791.1:c.3679C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382792.1:c.3652C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382793.1:c.3646C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382794.1:c.3646C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382795.1:c.3640C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382796.1:c.3601C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382797.1:c.3589C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382798.1:c.3532C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382799.1:c.3508C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382800.1:c.3502C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382801.1:c.3484C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382802.1:c.3430C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382804.1:c.2860C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382805.1:c.2737C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382806.1:c.2650C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004448.4:c.3688C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110535.2:n.3926C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Microthlaspi perfoliatum isolate Kz13_13_10 internal transcribed spacer 1, parti...
Microthlaspi perfoliatum isolate Kz13_13_10 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|1237407315|gb|KY318963.1|

Nucleotide
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Microthlaspi perfoliatum isolate Gr-1-6 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|1123434932|gb|KU293813.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002202862	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29072371, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002202862

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 15, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

HER2 exon 27 mutations predict worse survival of breast cancer patients, especially in HER2-negative patients.

Si P, Chen T, Fang B, Yao J, Liu G, Chen H, Zhai B, Li W.

Cancer Med. 2017 Dec;6(12):2832-2839. doi: 10.1002/cam4.1236. Epub 2017 Oct 26.

PubMed [citation]

PMID:: 29072371
PMCID:: PMC5727320

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, SCV002202862.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1230 of the ERBB2 protein (p.Arg1230Trp). This variant is present in population databases (rs769940977, gnomAD 0.005%). This missense change has been observed in individual(s) with breast cancer (PMID: 29072371). ClinVar contains an entry for this variant (Variation ID: 1428040). 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 disruptive. 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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