NM_004448.4(ERBB2):c.3661T>C (p.Tyr1221His) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 12, 2022
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:: RCV002598321.3

Allele description [Variation Report for NM_004448.4(ERBB2):c.3661T>C (p.Tyr1221His)]

NM_004448.4(ERBB2):c.3661T>C (p.Tyr1221His)

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.3661T>C (p.Tyr1221His)

HGVS:

NC_000017.11:g.39727937T>C
NG_007503.1:g.44798T>C
NM_001005862.3:c.3571T>C
NM_001289936.2:c.3616T>C
NM_001289937.2:c.*240T>C
NM_001382782.1:c.3571T>C
NM_001382783.1:c.3571T>C
NM_001382784.1:c.3778T>C
NM_001382785.1:c.3763T>C
NM_001382786.1:c.3742T>C
NM_001382787.1:c.3736T>C
NM_001382788.1:c.3691T>C
NM_001382789.1:c.3682T>C
NM_001382790.1:c.3658T>C
NM_001382791.1:c.3652T>C
NM_001382792.1:c.3625T>C
NM_001382793.1:c.3619T>C
NM_001382794.1:c.3619T>C
NM_001382795.1:c.3613T>C
NM_001382796.1:c.3574T>C
NM_001382797.1:c.3562T>C
NM_001382798.1:c.3505T>C
NM_001382799.1:c.3481T>C
NM_001382800.1:c.3475T>C
NM_001382801.1:c.3457T>C
NM_001382802.1:c.3403T>C
NM_001382803.1:c.*240T>C
NM_001382804.1:c.2833T>C
NM_001382805.1:c.2710T>C
NM_001382806.1:c.2623T>C
NM_004448.4:c.3661T>CMANE SELECT
NP_001005862.1:p.Tyr1191His
NP_001005862.1:p.Tyr1191His
NP_001276865.1:p.Tyr1206His
NP_001276865.1:p.Tyr1206His
NP_001369711.1:p.Tyr1191His
NP_001369712.1:p.Tyr1191His
NP_001369713.1:p.Tyr1260His
NP_001369714.1:p.Tyr1255His
NP_001369715.1:p.Tyr1248His
NP_001369716.1:p.Tyr1246His
NP_001369717.1:p.Tyr1231His
NP_001369718.1:p.Tyr1228His
NP_001369719.1:p.Tyr1220His
NP_001369720.1:p.Tyr1218His
NP_001369721.1:p.Tyr1209His
NP_001369722.1:p.Tyr1207His
NP_001369723.1:p.Tyr1207His
NP_001369724.1:p.Tyr1205His
NP_001369725.1:p.Tyr1192His
NP_001369726.1:p.Tyr1188His
NP_001369727.1:p.Tyr1169His
NP_001369728.1:p.Tyr1161His
NP_001369729.1:p.Tyr1159His
NP_001369730.1:p.Tyr1153His
NP_001369731.1:p.Tyr1135His
NP_001369733.1:p.Tyr945His
NP_001369734.1:p.Tyr904His
NP_001369735.1:p.Tyr875His
NP_004439.2:p.Tyr1221His
NP_004439.2:p.Tyr1221His
LRG_724t1:c.3571T>C
LRG_724t2:c.3661T>C
LRG_724t4:c.3616T>C
LRG_724:g.44798T>C
LRG_724p1:p.Tyr1191His
LRG_724p2:p.Tyr1221His
LRG_724p4:p.Tyr1206His
NC_000017.10:g.37884190T>C
NM_001005862.2:c.3571T>C
NM_001289936.1:c.3616T>C
NM_004448.3:c.3661T>C
NR_110535.2:n.3899T>C

Protein change:

Y1135H

Molecular consequence:

NM_001289937.2:c.*240T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001382803.1:c.*240T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001005862.3:c.3571T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001289936.2:c.3616T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382782.1:c.3571T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382783.1:c.3571T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382784.1:c.3778T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382785.1:c.3763T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382786.1:c.3742T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382787.1:c.3736T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382788.1:c.3691T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382789.1:c.3682T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382790.1:c.3658T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382791.1:c.3652T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382792.1:c.3625T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382793.1:c.3619T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382794.1:c.3619T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382795.1:c.3613T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382796.1:c.3574T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382797.1:c.3562T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382798.1:c.3505T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382799.1:c.3481T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382800.1:c.3475T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382801.1:c.3457T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382802.1:c.3403T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382804.1:c.2833T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382805.1:c.2710T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382806.1:c.2623T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004448.4:c.3661T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_110535.2:n.3899T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Homo sapiens partial CD3G gene, exon 3
Homo sapiens partial CD3G gene, exon 3
gi|36812|emb|X06028.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002955102	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 12, 2022)	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

SCV002955102

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 12, 2022)

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, SCV002955102.2

#	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 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 affected with ERBB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1221 of the ERBB2 protein (p.Tyr1221His).

#	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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