Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: Implications for genetic testing

Table 1 Characteristics of carrier families and Hungarian MMR gene mutations

ProbandID	Probandphenotype1	Familyphenotype2		Gene	Exon	Nucleotide position ofthe mutation	Effect/Consequence of themutation
HFC003	C25	AI:	9C, 1E	MLH1	2	c.187G>A	p.D63N
HFC077	C53	AI:	3C, 1S	MLH1	16	c.1852_1854del	p.K618del
HFC100	C39	AI:	5C, 3S, 1E	MLH1	18-19	c.2078_2172del	p.E693_K724delAfsX8
HFC075	C33	AI:	3C	MSH2	1-2	c.1-?_c.366+?del	no protein?
HFC048	C31	AI:	6C	MSH2	3-7	c.367-?_c.1226+?del	deletion of exons 3-7
HFC066	C22	AI:	6C, 1S	MSH2	4	c.759_762del	p.M253_N254delIfsX20
HFC108	C30	AI:	5C, 1E	MSH2	7	c.1226_1227del	p.Q409RfsX7
HFC014	C29	AI:	3C	MSH2	10	c.1661+1G>T	splice defect?
HFC021	C47	AI:	3C	MSH2	13	c.2131C>T	p.R711X
HFC050	C36	AII:	2C, 1I	MLH1	8	c.677G>A	p.R226Q
HFC045	C19	AII:	2C, 1E	MLH1	13	c.1489_1490insC	p.R497fsX6
HFE063	E47	AII:	1C, 2E	MLH1	16	c.1875T>G	p.Y625X
MPX050	C36	AII:	2C, 2S, 1E, 1I	MLH1	19	c.2141G>A	p.W714X
HFC017	C27	AII:	3C, 3E	MSH2	12	c.1861C>T	p.R621X
HFC072	C35	SH:	1C	MLH1	13	c.1411_1414del	p.K471_R472delDfsX19
HFC104	C39	SH:	2C	MLH1	16	c.1852_1853delinsGC	p.K618A
HFC078	C53	SH:	1C	MSH2	1	c.146A>T	p.D49V
HFC074	C45, 50, 55	SH:	4C	MSH2	15	c.2620_2621ins115	p.Y874CfsX3

¹Cancer type and age at onset (C: colorectal; E: endometrial);

²Categories according to the Amsterdam criteria (AI: AmsterdamI; AII: Amsterdam II; SH: suspected HNPCC) and number and type of cancer in the family (C: colorectal; E: endometrial; S: stomach;I: intestinal). Novel mutations are in bold.

Table 2 Frequency of pathogenic or unclassified sequence variants in Hungarian HNPCC and suspected HNPCC families

	Frequency of variant (%)
	Pathogenic	Unclassified	Total
HNPCC (AmsterdamI+ II)	13/20 (65)	1/20 (5)	14/20 (70)
Suspected HNPCC	3/16 (19)	1/16 (6)	4/16 (25)
Total	16/36 (44)	2/36 (6)	18/36 (50)