NM_004448.4(ERBB2):c.3428C>T (p.Pro1143Leu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 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:: RCV002515853.2

Allele description [Variation Report for NM_004448.4(ERBB2):c.3428C>T (p.Pro1143Leu)]

NM_004448.4(ERBB2):c.3428C>T (p.Pro1143Leu)

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.3428C>T (p.Pro1143Leu)

HGVS:

NC_000017.11:g.39727704C>T
NG_007503.1:g.44565C>T
NM_001005862.3:c.3338C>T
NM_001289936.2:c.3383C>T
NM_001289937.2:c.*7C>T
NM_001382782.1:c.3338C>T
NM_001382783.1:c.3338C>T
NM_001382784.1:c.3545C>T
NM_001382785.1:c.3530C>T
NM_001382786.1:c.3509C>T
NM_001382787.1:c.3503C>T
NM_001382788.1:c.3458C>T
NM_001382789.1:c.3449C>T
NM_001382790.1:c.3425C>T
NM_001382791.1:c.3419C>T
NM_001382792.1:c.3392C>T
NM_001382793.1:c.3386C>T
NM_001382794.1:c.3386C>T
NM_001382795.1:c.3380C>T
NM_001382796.1:c.3341C>T
NM_001382797.1:c.3329C>T
NM_001382798.1:c.3272C>T
NM_001382799.1:c.3248C>T
NM_001382800.1:c.3242C>T
NM_001382801.1:c.3224C>T
NM_001382802.1:c.3170C>T
NM_001382803.1:c.*7C>T
NM_001382804.1:c.2600C>T
NM_001382805.1:c.2477C>T
NM_001382806.1:c.2390C>T
NM_004448.4:c.3428C>TMANE SELECT
NP_001005862.1:p.Pro1113Leu
NP_001276865.1:p.Pro1128Leu
NP_001369711.1:p.Pro1113Leu
NP_001369712.1:p.Pro1113Leu
NP_001369713.1:p.Pro1182Leu
NP_001369714.1:p.Pro1177Leu
NP_001369715.1:p.Pro1170Leu
NP_001369716.1:p.Pro1168Leu
NP_001369717.1:p.Pro1153Leu
NP_001369718.1:p.Pro1150Leu
NP_001369719.1:p.Pro1142Leu
NP_001369720.1:p.Pro1140Leu
NP_001369721.1:p.Pro1131Leu
NP_001369722.1:p.Pro1129Leu
NP_001369723.1:p.Pro1129Leu
NP_001369724.1:p.Pro1127Leu
NP_001369725.1:p.Pro1114Leu
NP_001369726.1:p.Pro1110Leu
NP_001369727.1:p.Pro1091Leu
NP_001369728.1:p.Pro1083Leu
NP_001369729.1:p.Pro1081Leu
NP_001369730.1:p.Pro1075Leu
NP_001369731.1:p.Pro1057Leu
NP_001369733.1:p.Pro867Leu
NP_001369734.1:p.Pro826Leu
NP_001369735.1:p.Pro797Leu
NP_004439.2:p.Pro1143Leu
LRG_724:g.44565C>T
NC_000017.10:g.37883957C>T
NR_110535.2:n.3666C>T

Protein change:

P1057L

Links:

dbSNP: rs587778269

NCBI 1000 Genomes Browser:

rs587778269

Molecular consequence:

NM_001289937.2:c.*7C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001382803.1:c.*7C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001005862.3:c.3338C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001289936.2:c.3383C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382782.1:c.3338C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382783.1:c.3338C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382784.1:c.3545C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382785.1:c.3530C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382786.1:c.3509C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382787.1:c.3503C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382788.1:c.3458C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382789.1:c.3449C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382790.1:c.3425C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382791.1:c.3419C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382792.1:c.3392C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382793.1:c.3386C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382794.1:c.3386C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382795.1:c.3380C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382796.1:c.3341C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382797.1:c.3329C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382798.1:c.3272C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382799.1:c.3248C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382800.1:c.3242C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382801.1:c.3224C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382802.1:c.3170C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382804.1:c.2600C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382805.1:c.2477C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382806.1:c.2390C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004448.4:c.3428C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110535.2:n.3666C>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
SCV003503792	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 15, 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

SCV003503792

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 15, 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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003503792.2

#	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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 134081). This variant has not been reported in the literature in individuals affected with ERBB2-related conditions. This variant is present in population databases (rs587778269, gnomAD 0.009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1143 of the ERBB2 protein (p.Pro1143Leu).

#	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