Table 10. [Lynch Syndrome: Notable Pathogenic Variants by Gene]. - GeneReviews®

Gene ¹	Reference Sequences	DNA Nucleotide Change	Predicted Protein Change	Comment / Population ²
EPCAM	NM_002354.2	c.859-1462_*1999del4909 (del exons 8-9)	--	Netherlands
c.858+2478_*4507del8674 (del exons 8-9)	--
c.858+2568_*4596del8673 (del exons 8-9)	--	Spain
c.858+2488_*7469del11626 (del exons 8-9)	--
c.859-1860_25547del (EPCAM* del exons 8-9 & MSH2 del exons 1-3)	--
c.859–1430_*2033del (del exons 8-9)	--	Italy
MLH1	NM_000249.3 NP_000240.1	c.1731+2247_1897-402del (del exon 16)	p.Pro579_Glu633del	Finland
NM_000249.3	c.454-1G>A	--
NM_000249.3 NP_000240.1	c.112A>C	p.Asn38His	Netherlands
NM_000249.3	c.306+5G>A	--	Spain; variants are assoc w/moderate penetrance.
NM_000249.3 NP_000240.1	c.1865T>A	p.Leu622His
NM_000249.3	c.1896+280_8935del11626 (MLH1* del exons 17-19 & LRRFIP2 del exons 26-29)	--	Portugal
c.545+3A>G	--	Italy, Canada-Quebec (persons of Italian ancestry) & Brazil
c.589-2A>G	--	United States & Italy
NM_000249.3 NP_000240.1	c.731G>A	p.Gly244Asp	Italy
NM_000249.3	c.1558+1G>T	--
NM_000249.3 NP_000240.1	c.2252_2253delAA	p.Lys751SerfsTer3
c.2269dupT	p.(*757LeuextTer33)
c.1731G>A	p.Ser556ArgfsTer14
c.1489dupC	p.Arg497ProfsTer6	Germany
NM_000249.3	c.1667+2_1667+8delTAAATCAinsATTT	–	Denmark
NM_000249.3 NP_000240.1	c.2142G>A	p.Trp714Ter	Switzerland
c.2195_2198dupAACA	p.His733GlnfsTer14	Canada-Quebec
c.1831_1832delAT	p.Ile611CysfsTer2
c.1039-2329_1409+827del3527	p.Thr347LysfsTer8
c.1381A>T	p.Lys461Ter	United States
c.2044_2045delAT	p.Met682ValfsTer11	Puerto Rico
c.392C>G	p.Ser131Ter	Republic of Macedonia
NM_000249.3	1.8-kb deletion of exon 11	--	China
NM_000249.3 NP_000240.1	c.793C>T	p.Arg265Cys	Taiwan
c.1758dupC	p.Met587HisfsTer6	Korea
MSH2	NM_000251.2	c.942+3A>T	--	Common worldwide
NM_000251.2 NP_000242.1	c.388_389delCA	p.Gln130ValfsTer2	Portugal, South America
c.2152C>T	p.Gln718Ter	Portugal
c.2063T>G	p.Met688Arg	Spain
NM_000251.2	c.[2635-3C>T; 2635-5T>C]	--
c.-3568_*28336del36681 (del exons 4-8)	--
c.4136_13502del9366 (del exon 7)	--
c.-11844_1077-6021delins(155) (del exons 1-6)	--	Italy
c.1277−1180_1386+2226del3516insCATTCTCTTTGAAAA) (del exon 8)	--
c.1276+198_1386+3761del19280 (del exon 8)	--
NM_000251.2 NP_000242.1	c.1786_1788delAAT	p.Asn596del	Denmark
NM_000251.2	c.-823_1076+5984del (del exons 1-6)	–	United States
NM_000251.2 NP_000242.1	c.1906G>C	p.Ala636Pro	Ashkenazi Jews
c.1165C>T	p.Arg389Ter	Canada-Quebec
c.2185_2192delATGTTGGAinsCCCT	p.Met729ProfsTer2	Chile
c.1457_1460delATGA	p.Asn486fsTer10	China (Guangdong)
MSH6	NM_000179.2 NP_000170.1	c.467C>G	p.Ser156Ter	Netherlands
c.651dupT	p.Lys218Ter
c.1614_1615delTCinsAG	p.Tyr538Ter
c.2983G>T	p.Glu995Ter	Finland
c.1346T>C	p.Leu449Pro	Sweden
c.2931C>G	p.Tyr977Ter
c.3959_3962delCAAG	p.Ala1320GlufsTer6	Ashkenazi Jews
c.3984_3987dupGTCA	p.Leu1330ValfsTer12
PMS2	NM_000535.6	c.989-1G>T	--	Norway
NM_000535.6 NP_000526.2	c.736_741delCCCCCTins11	p.Pro246CysfsTer3	United States
c.137G>T	p.Ser46Ile	United States
c.1A>G	p.Met1?
c.903G>T	p.Lys301Asn
c.989-296_1144+706del1158 (del exon 10)	p.Glu330_Glu381del	Australia
c.2002A>G	p.Ile668Val	Inuit

Gene ¹

Reference Sequences

DNA Nucleotide Change

Predicted Protein Change

Comment / Population ²

EPCAM

NM_002354.2

c.859-1462_*1999del4909
(del exons 8-9)

Netherlands

c.858+2478_*4507del8674
(del exons 8-9)

c.858+2568_*4596del8673
(del exons 8-9)

Spain

c.858+2488_*7469del11626
(del exons 8-9)

c.859-1860_*25547del
(EPCAM del exons 8-9 & MSH2 del exons 1-3)

c.859–1430_*2033del
(del exons 8-9)

Italy

MLH1

NM_000249.3
NP_000240.1

c.1731+2247_1897-402del
(del exon 16)

p.Pro579_Glu633del

Finland

NM_000249.3

c.454-1G>A

NM_000249.3
NP_000240.1

c.112A>C

p.Asn38His

Netherlands

NM_000249.3

c.306+5G>A

Spain; variants are assoc w/moderate penetrance.

NM_000249.3
NP_000240.1

c.1865T>A

p.Leu622His

NM_000249.3

c.1896+280_*8935del11626
(MLH1 del exons 17-19 & LRRFIP2 del exons 26-29)

Portugal

c.545+3A>G

Italy, Canada-Quebec (persons of Italian ancestry) & Brazil

c.589-2A>G

United States & Italy

NM_000249.3
NP_000240.1

c.731G>A

p.Gly244Asp

Italy

NM_000249.3

c.1558+1G>T

NM_000249.3
NP_000240.1

c.2252_2253delAA

p.Lys751SerfsTer3

c.2269dupT

p.(*757LeuextTer33)

c.1731G>A

p.Ser556ArgfsTer14

c.1489dupC

p.Arg497ProfsTer6

Germany

NM_000249.3

c.1667+2_1667+8delTAAATCAinsATTT

–

Denmark

NM_000249.3
NP_000240.1

c.2142G>A

p.Trp714Ter

Switzerland

c.2195_2198dupAACA

p.His733GlnfsTer14

Canada-Quebec

c.1831_1832delAT

p.Ile611CysfsTer2

c.1039-2329_1409+827del3527

p.Thr347LysfsTer8

c.1381A>T

p.Lys461Ter

United States

c.2044_2045delAT

p.Met682ValfsTer11

Puerto Rico

c.392C>G

p.Ser131Ter

Republic of Macedonia

NM_000249.3

1.8-kb deletion of exon 11

China

NM_000249.3
NP_000240.1

c.793C>T

p.Arg265Cys

Taiwan

c.1758dupC

p.Met587HisfsTer6

Korea

MSH2

NM_000251.2

c.942+3A>T

Common worldwide

NM_000251.2
NP_000242.1

c.388_389delCA

p.Gln130ValfsTer2

Portugal, South America

c.2152C>T

p.Gln718Ter

Portugal

c.2063T>G

p.Met688Arg

Spain

NM_000251.2

c.[2635-3C>T; 2635-5T>C]

c.-3568_*28336del36681
(del exons 4-8)

c.*4136_*13502del9366
(del exon 7)

c.-11844_1077-6021delins(155)
(del exons 1-6)

Italy

c.1277−1180_1386+2226del3516insCATTCTCTTTGAAAA)
(del exon 8)

c.1276+198_1386+3761del19280
(del exon 8)

NM_000251.2
NP_000242.1

c.1786_1788delAAT

p.Asn596del

Denmark

NM_000251.2

c.-823_1076+5984del
(del exons 1-6)

–

United States

NM_000251.2
NP_000242.1

c.1906G>C

p.Ala636Pro

Ashkenazi Jews

c.1165C>T

p.Arg389Ter

Canada-Quebec

c.2185_2192delATGTTGGAinsCCCT

p.Met729ProfsTer2

Chile

c.1457_1460delATGA

p.Asn486fsTer10

China (Guangdong)

MSH6

NM_000179.2
NP_000170.1

c.467C>G

p.Ser156Ter

Netherlands

c.651dupT

p.Lys218Ter

c.1614_1615delTCinsAG

p.Tyr538Ter

c.2983G>T

p.Glu995Ter

Finland

c.1346T>C

p.Leu449Pro

Sweden

c.2931C>G

p.Tyr977Ter

c.3959_3962delCAAG

p.Ala1320GlufsTer6

Ashkenazi Jews

c.3984_3987dupGTCA

p.Leu1330ValfsTer12

PMS2

NM_000535.6

c.989-1G>T

Norway

NM_000535.6
NP_000526.2

c.736_741delCCCCCTins11

p.Pro246CysfsTer3

United States

c.137G>T

p.Ser46Ile

United States

c.1A>G

p.Met1?

c.903G>T

p.Lys301Asn

c.989-296_1144+706del1158
(del exon 10)

p.Glu330_Glu381del

Australia

c.2002A>G

p.Ile668Val

Inuit

From: Lynch Syndrome

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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