NM_004448.4(ERBB2):c.3541G>A (p.Val1181Ile) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 22, 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:: RCV002615242.3

Allele description [Variation Report for NM_004448.4(ERBB2):c.3541G>A (p.Val1181Ile)]

NM_004448.4(ERBB2):c.3541G>A (p.Val1181Ile)

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.3541G>A (p.Val1181Ile)

HGVS:

NC_000017.11:g.39727817G>A
NG_007503.1:g.44678G>A
NM_001005862.3:c.3451G>A
NM_001289936.2:c.3496G>A
NM_001289937.2:c.*120G>A
NM_001382782.1:c.3451G>A
NM_001382783.1:c.3451G>A
NM_001382784.1:c.3658G>A
NM_001382785.1:c.3643G>A
NM_001382786.1:c.3622G>A
NM_001382787.1:c.3616G>A
NM_001382788.1:c.3571G>A
NM_001382789.1:c.3562G>A
NM_001382790.1:c.3538G>A
NM_001382791.1:c.3532G>A
NM_001382792.1:c.3505G>A
NM_001382793.1:c.3499G>A
NM_001382794.1:c.3499G>A
NM_001382795.1:c.3493G>A
NM_001382796.1:c.3454G>A
NM_001382797.1:c.3442G>A
NM_001382798.1:c.3385G>A
NM_001382799.1:c.3361G>A
NM_001382800.1:c.3355G>A
NM_001382801.1:c.3337G>A
NM_001382802.1:c.3283G>A
NM_001382803.1:c.*120G>A
NM_001382804.1:c.2713G>A
NM_001382805.1:c.2590G>A
NM_001382806.1:c.2503G>A
NM_004448.4:c.3541G>AMANE SELECT
NP_001005862.1:p.Val1151Ile
NP_001005862.1:p.Val1151Ile
NP_001276865.1:p.Val1166Ile
NP_001276865.1:p.Val1166Ile
NP_001369711.1:p.Val1151Ile
NP_001369712.1:p.Val1151Ile
NP_001369713.1:p.Val1220Ile
NP_001369714.1:p.Val1215Ile
NP_001369715.1:p.Val1208Ile
NP_001369716.1:p.Val1206Ile
NP_001369717.1:p.Val1191Ile
NP_001369718.1:p.Val1188Ile
NP_001369719.1:p.Val1180Ile
NP_001369720.1:p.Val1178Ile
NP_001369721.1:p.Val1169Ile
NP_001369722.1:p.Val1167Ile
NP_001369723.1:p.Val1167Ile
NP_001369724.1:p.Val1165Ile
NP_001369725.1:p.Val1152Ile
NP_001369726.1:p.Val1148Ile
NP_001369727.1:p.Val1129Ile
NP_001369728.1:p.Val1121Ile
NP_001369729.1:p.Val1119Ile
NP_001369730.1:p.Val1113Ile
NP_001369731.1:p.Val1095Ile
NP_001369733.1:p.Val905Ile
NP_001369734.1:p.Val864Ile
NP_001369735.1:p.Val835Ile
NP_004439.2:p.Val1181Ile
NP_004439.2:p.Val1181Ile
LRG_724t1:c.3451G>A
LRG_724t2:c.3541G>A
LRG_724t4:c.3496G>A
LRG_724:g.44678G>A
LRG_724p1:p.Val1151Ile
LRG_724p2:p.Val1181Ile
LRG_724p4:p.Val1166Ile
NC_000017.10:g.37884070G>A
NM_001005862.2:c.3451G>A
NM_001289936.1:c.3496G>A
NM_004448.3:c.3541G>A
NR_110535.2:n.3779G>A

Protein change:

V1095I

Molecular consequence:

NM_001289937.2:c.*120G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001382803.1:c.*120G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001005862.3:c.3451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001289936.2:c.3496G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382782.1:c.3451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382783.1:c.3451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382784.1:c.3658G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382785.1:c.3643G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382786.1:c.3622G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382787.1:c.3616G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382788.1:c.3571G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382789.1:c.3562G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382790.1:c.3538G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382791.1:c.3532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382792.1:c.3505G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382793.1:c.3499G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382794.1:c.3499G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382795.1:c.3493G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382796.1:c.3454G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382797.1:c.3442G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382798.1:c.3385G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382799.1:c.3361G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382800.1:c.3355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382801.1:c.3337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382802.1:c.3283G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382804.1:c.2713G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382805.1:c.2590G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382806.1:c.2503G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004448.4:c.3541G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_110535.2:n.3779G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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GBE1 [Mesitornis unicolor]
Gene ID:104534741

Gene
PLA2G4A [Zalophus californianus]
PLA2G4A [Zalophus californianus]
Gene ID:113933605

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003497237	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 22, 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

SCV003497237

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 22, 2023)

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, SCV003497237.2

#	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 valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1181 of the ERBB2 protein (p.Val1181Ile). This variant is present in population databases (rs776754071, gnomAD 0.002%). 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: 2179817). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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

ClinVar

Relating variation to medicine