Table 3.

Variants of Uncertain Significance Detected in Patients With MMR-Deficient Rectal Cancer: Clinical Characteristics and In Silico Analysis at RNA and Protein Levels

Pt	Gene	DNA Change	Protein Change	Mut	In Silico RNA Analysis		In Silico Protein Analysis			Age at Dx (years)	Sex	Other CA	Stage at Dx	Ams	Beth	PREMM1,2,6 Score	VS	FU (years)
					NNSplice22	SplicePort24	PP223	FATH-MM25	Mut Taster26
1	MLH1	c.110A>G	p.E37G	Ms	NE	NE	PrD	D	D	65	F	Endometrial	cT4N0M0	Yes	Yes	88.3	A	10.8
2	MLH1	c.1958T>G	p.L653R	Ms	NE	AbSS	PrD	D	D	41	M	Colon	cT3N0M0	No	Yes	74	A	5.1
3	MSH2	c.328A>C	p.K110Q	Ms	NE	NE	PrD	D	D	36	M	Colon	cT4N1M0	No	Yes	28.5	A	11.8
4	MSH2	c.2030C>G	p.T677R	Ms	NE	NE	PrD	D	D	45	F	None	cT3N1M0	No	Yes	3.8	A	9
5	MSH2	c.2234T>G	p.I745R	Ms	NE	NE	PrD	D	D	46	F	Endometrial	cT1N0M0	No	Yes	19.5	A	9.7
6	MSH2	c.2320A>G	p.I774V	Ms	AbSS	AbSS	PsD	D	D	30	M	Osteosarcoma	cT3N1M0	No	Yes	33.3	A	8.2
7	MSH6	c.2600T>G	p.V867G	Ms	NE	NE	Neu	D	D	41	M	None	cT4N2M0	No	Yes	8	A	3.3

NOTE. The variants may be classified as likely pathogenic if one or two programs at the RNA levels predicted aberrant splicing or two or more programs at the protein level predicted damaging (Data Supplement, Method).

Abbreviations: A, alive; AbSS, aberrant splicing site; Ams, Amsterdam I or II; Beth, Bethesda; CA, cancer; D, damaging; Dx, diagnosis; FU, follow-up; Ms, missense; Mut, mutation; NE, no effect; Neu, neutral; PP2, polyphen2 (HumVar); PrD, probably damaging; PsD, possibly damaging; Pt, patient; SS, splicing site; VS, vital status.