Table 1.

SOS1 Exonic Indels and Missense Changes Identified in the Study

Exon	Nucleotide change	Amino acid change	Domain	Notes	Number of cases
Mutations
4	c.322G>A	p.Glu108Lys	HF		2, fam.unknown
5	c.508A>G	p.Lys170Glu	HF		1, sporadic; 2, fam.unknown
7	c.797C>A	p.Thr266Lys	DH		1, sporadic; 3, fam.unknown
7	c.806T>C	p.Met269Thr	DH		3, sporadic; 2, fam.unknown
7	c.806T>G	p.Met269Arg	DH		1, fam.unknown
11	c.1281_1289delGAATATTGA	p.Lys427_Asp430delinsAsn	PH		1, fam.unknown
11	c.1294T>C	p.Trp432Arg	PH		1, sporadic; 1, fam.unknown
11	c.1294_1299delTGGGAG	p.Trp432_Glu433del	PH	CTRL, NPS	1, sporadic
11	c.1297G>A	p.Glu433Lys	PH		3, sporadic; 3, fam.unknown
11	c.1300G>A	p.Gly434Arg	PH		2, fam.unknown
11	c.1300_1301delGGinsAA	p.Gly434Lys	PH	de novo, PPhen+, SIFT+, CON	1, sporadic
11	c.1310T>C	p.Ile437Thr	PH	de novo, PPhen++, SIFT+, CON	1, sporadic; 1, familial
11	c.1322G>A	p.Cys441Tyr	PH		1, fam.unknown
11	c.1430A>G	p.Gln477Arg	PH	PPhen−, SIFT−, CON	2, fam.unknown
11	c.1433C>G	p.Pro478Arg	PH		1, sporadic
11	c.1642A>C	p.Ser548Arg	PH-REM linker		4, fam.unknown
11	c.1654A>G	p.Arg552Gly	PH-REM linker		3, sporadic; 8, fam.unknown
11	c.1655G>A	p.Arg552Lys	PH-REM linker		2, sporadic; 2, fam.unknown
11	c.1655G>T	p.Arg552Met	PH-REM linker	NPS, PPhen++, SIFT+, CON	2, sporadic
11	c.1655G>C	p.Arg552Thr	PH-REM linker		1, fam.unknown
11	c.1656G>C	p.Arg552Ser	PH-REM linker		2, sporadic; 7, fam.unknwn
11	c.1660_1673delCTTGATGTAACAATinsAA	p.Leu554_Met558delinsLys	PH-REM linker		1, fam.unknown
15	c.2197A>T	p.Ile733Phe	REM		1, fam.unknown
17	c.2536G>A	p.Glu846Lys	CDC25		1, sporadic, 6 fam.unknown
18	c.2681C>G	p.Pro894Arg	CDC25	CTRL, PPhen+, SIFT−, CON	1, familiala
Possibly pathogenic variants
4	c.335C>G	p.Pro112Arg	HF	NPS, PPhen+, SIFT−	1, sporadic
7	c.755T>C	p.Ile252Thr	DH	CTRL, PPhen++, SIFT+, CON	1, familial
11	c.1264A>G	p.Met422Val	PH	PPhen++, SIFT−; CON	1, fam.unknown
11	c.1270G>A	p.Glu424Lys	PH	PPhen+, SIFT+, CON	1, fam.unknown
11	c.1444G>C	p.Gly482Arg	PH	PPhen+, SIFT+, CON	1, fam.unknown
11	c.1469T>G	p.Leu490Arg	PH	CTRL, NPS, PPhen++, SIFT+, CON	1, sporadic
11	c.1490G>A	p.Arg497Gln	PH	CTRL, PPhen+, SIFT+, CON	1, sporadicb
11	c.1646C>A	p.Thr549Lys	PH-REM linker	PPhen+, SIFT−, CON	1, fam.unknown
Unclassified variants
3	c.109A>G	p.Thr37Ala	HF	PPhen−, SIFT−, CON	1, fam.unknown
11	c.1433C>T	p.Pro478Leu	PH	PPhen+, SIFT-, CON	1, fam.unknown
15	c.2351T>C	p.Ile784Thr	REM	PPhen++, SIFT+, CON	1, fam.unknownc
23	c.3392G>A	p.Arg1131Lys	C-terminus	PPhen−, SIFT−, CON	1, fam.unknown
23	c.3418T>A	p.Leu1140Ile	C-terminus	PPhen−, SIFT−, CON	1, fam.unknown
24	c.3769A>G	p.Thr1257Ala	C-terminus	PPhen−, SIFT−, CON	1, fam.unknown

Nucleotide numbering reflects cDNA numbering with 1 corresponding to the A of the ATG translation initiation codon in the reference sequence (NM_005633.3). Exon 2 corresponds to the first protein coding exon. Novel mutations are in bold.

^aVariant inherited from an affected parent.

^bVariant inherited from an apparently unaffected parent.

^cVariant concomitant with the disease-causing p.Met269Arg change.

HF, histone folds; DH, DBL homology domain; PH, plekstrin homology domain; REM, RAS exchanger motif, CDC25, CDC25 domain. Fam.unknown, familial status unknown; NPS, unavailable parental DNA samples. CTRL, variant not occurring in ≥300 population-matched unaffected subjects; de novo, variant demonstrated to occur de novo by DNA genotyping of unaffected parents; PPhen++, amino acid change predicted to be “probably damaging” by PolyPhen; PPhen+, amino acid change predicted to be “possibly damaging” by PolyPhen; PPhen−, amino acid change predicted to be “benign” by Polyphen; SIFT+, amino acid change predicted to “affect protein function” by SIFT; SIFT−, amino acid change predicted to be “tolerated” by SIFT; CON, variant at a conserved residue.