Variant · Insertion

ERBB2 Y772_A775DUP

CI-VAR-00004845Explore in graph →NM_001005862.2:c.2224_2235dupTACGTGATGGCTClinVar 44985 CIViC 414 rs397516977

Curated evidence

Evidence by cancer (10 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–10 of 10 evidence items across 4 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Lung Adenocarcinoma4
ERBB2 Y772_A775DUP	Afatinib	Predictive	C	Supports Sensitivity Response	4	accepted	EID1045 A 55 year old heavily pretreated patient with equivocal HER2 overexpression (IHC2+ and no amplification in FISH) was found to have the HER2 YMVA kinase domain insertion. Afatinib monotherapy resulted… (full text at CIViC) PMID 26559459 · Li et al., 2015 · Open in CIViC	civic
ERBB2 Y772_A775DUP	Afatinib	Predictive	C	Supports Sensitivity Response	3	accepted	EID1888 A Phase II study for use of Afatinib in non- or light smokers with lung adenocarcinoma. Three patients with metastatic lung adenocarcinomas bearing mutations in the kinase domain of HER2 gene were ide… (full text at CIViC) PMID 22325357 · De Grève et al., 2012 · Open in CIViC	civic

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
44985	Likely pathogenic	criteria provided, single submitter	1	Non-small cell lung carcinoma; Lung adenocarcinoma	somatic	2	Mar 11, 2011	clinvar

Lung Adenosquamous Carcinoma1
ERBB2 Y772_A775DUP	Afatinib	Predictive	D	Supports Sensitivity Response	4	accepted	EID1047 Human HER2 with YVMA insertion was put under a clara cell specific, rtTA promoter system inducible via doxycycline. Induction of mutant HER2 in these mice drove rapid development of adenosquamous lung… (full text at CIViC) PMID 19122144 · Perera et al., 2009 · Open in CIViC	civic

Lung Adenosquamous Carcinoma1

ERBB2 Y772_A775DUP

Afatinib

Predictive

Supports Sensitivity Response

accepted

EID1047

Human HER2 with YVMA insertion was put under a clara cell specific, rtTA promoter system inducible via doxycycline. Induction of mutant HER2 in these mice drove rapid development of adenosquamous lung… (full text at CIViC)

PMID 19122144 · Perera et al., 2009 · Open in CIViC

civic

Lung Carcinoma1
ERBB2 Y772_A775DUP	Afatinib + SirolimusCombination	Predictive	D	Supports Sensitivity Response	4	rejected	EID1046 In mice, human HER2 with YVMA insertion was placed under a doxycycline-inducible, clara cell specific promoter. Induction of mutant HER2 in these mice drove rapid development of adenosquamous lung tum… (full text at CIViC) PMID 19122144 · Perera et al., 2009 · Open in CIViC	civic

Lung Carcinoma1

ERBB2 Y772_A775DUP

Afatinib + SirolimusCombination

Predictive

Supports Sensitivity Response

rejected

EID1046

In mice, human HER2 with YVMA insertion was placed under a doxycycline-inducible, clara cell specific promoter. Induction of mutant HER2 in these mice drove rapid development of adenosquamous lung tum… (full text at CIViC)

PMID 19122144 · Perera et al., 2009 · Open in CIViC

civic

Lung Non-Small Cell Carcinoma4
ERBB2 Y772_A775DUP	Afatinib + SirolimusCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID960 In preclinical studies of transgenic mice and xenografts, continuous expression of mutant ERBB2 (M774insAYVM or the equivalent A775insYVMA) was found to be essential for tumor maintenance. Furthermore… (full text at CIViC) PMID 19122144 · Perera et al., 2009 · Open in CIViC	civic
ERBB2 Y772_A775DUP	Bosutinib	Predictive	D	Supports Sensitivity Response	—	submitted	EID4428 In an in vitro study, ERBB2 A775_G776insYVMA mutation was associated with increased sensitivity to bosutinib treatment (IC50: 0.023�M vs. 3.7�M), as compared to wild-type ERBB2. Sensitivity was determ… (full text at CIViC) PMID 27491651 · Yu et al., 2016 · Open in CIViC	civic
ERBB2 Y772_A775DUP	Dacomitinib	Predictive	B	Does Not Support Sensitivity Response	2	accepted	EID1893 Phase 2 trial of ERBB-inhibitor dacomitinib in stage IIIB/IV lung cancers with HER2 mutations or amplification (N=30). Thirteen tumors harbored identical 12 base pair exon 20 insertions [A775_G776insY… (full text at CIViC) PMID 25899785 · Kris et al., 2015 · Open in CIViC	civic
ERBB2 Y772_A775DUP	Trastuzumab Deruxtecan	Predictive	A	Supports Sensitivity Response	4	accepted	EID11764 In a phase 2 trial, 152 metastatic NSCLC patients harboring mutations in ERBB2 (HER2) treated with 2 different doses of the HER2 ADC trastuzumab deruxtecan (5.4 mg/kg and 6.4 mg/kg) resulted in clinic… (full text at CIViC) PMID 37694347 · Goto et al., 2023 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma4

ERBB2 Y772_A775DUP

Afatinib + SirolimusCombination

Predictive

Supports Sensitivity Response

accepted

EID960

In preclinical studies of transgenic mice and xenografts, continuous expression of mutant ERBB2 (M774insAYVM or the equivalent A775insYVMA) was found to be essential for tumor maintenance. Furthermore… (full text at CIViC)

PMID 19122144 · Perera et al., 2009 · Open in CIViC

civic

ERBB2 Y772_A775DUP

Bosutinib

Predictive

Supports Sensitivity Response

—

submitted

EID4428

In an in vitro study, ERBB2 A775_G776insYVMA mutation was associated with increased sensitivity to bosutinib treatment (IC50: 0.023�M vs. 3.7�M), as compared to wild-type ERBB2. Sensitivity was determ… (full text at CIViC)

PMID 27491651 · Yu et al., 2016 · Open in CIViC

civic

ERBB2 Y772_A775DUP

Dacomitinib

Predictive

Does Not Support Sensitivity Response

accepted

EID1893

Phase 2 trial of ERBB-inhibitor dacomitinib in stage IIIB/IV lung cancers with HER2 mutations or amplification (N=30). Thirteen tumors harbored identical 12 base pair exon 20 insertions [A775_G776insY… (full text at CIViC)

PMID 25899785 · Kris et al., 2015 · Open in CIViC

civic

ERBB2 Y772_A775DUP

Trastuzumab Deruxtecan

Predictive

Supports Sensitivity Response

accepted

EID11764

In a phase 2 trial, 152 metastatic NSCLC patients harboring mutations in ERBB2 (HER2) treated with 2 different doses of the HER2 ADC trastuzumab deruxtecan (5.4 mg/kg and 6.4 mg/kg) resulted in clinic… (full text at CIViC)

PMID 37694347 · Goto et al., 2023 · Open in CIViC

civic