TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24910	74953;74954;74955	chr2:178571404;178571403;178571402	chr2:179436131;179436130;179436129
N2AB	23269	70030;70031;70032	chr2:178571404;178571403;178571402	chr2:179436131;179436130;179436129
N2A	22342	67249;67250;67251	chr2:178571404;178571403;178571402	chr2:179436131;179436130;179436129
N2B	15845	47758;47759;47760	chr2:178571404;178571403;178571402	chr2:179436131;179436130;179436129
Novex-1	15970	48133;48134;48135	chr2:178571404;178571403;178571402	chr2:179436131;179436130;179436129
Novex-2	16037	48334;48335;48336	chr2:178571404;178571403;178571402	chr2:179436131;179436130;179436129
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-69
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2869
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
G/A	None	None	0.63	N	0.514	0.247	0.276482976112	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	6.17284E-04	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
G/A	0.3065	likely_benign	0.2686	benign	-0.787	Destabilizing	0.63	D	0.514	neutral	N	0.492066706	None	None	I
G/C	0.5238	ambiguous	0.4701	ambiguous	-1.218	Destabilizing	0.999	D	0.713	prob.delet.	D	0.528328122	None	None	I
G/D	0.8037	likely_pathogenic	0.7337	pathogenic	-1.574	Destabilizing	0.967	D	0.615	neutral	N	0.516707933	None	None	I
G/E	0.7617	likely_pathogenic	0.7034	pathogenic	-1.64	Destabilizing	0.975	D	0.595	neutral	None	None	None	None	I
G/F	0.843	likely_pathogenic	0.8358	pathogenic	-1.197	Destabilizing	0.987	D	0.723	prob.delet.	None	None	None	None	I
G/H	0.8648	likely_pathogenic	0.8304	pathogenic	-1.244	Destabilizing	0.154	N	0.471	neutral	None	None	None	None	I
G/I	0.7247	likely_pathogenic	0.7126	pathogenic	-0.492	Destabilizing	0.975	D	0.737	prob.delet.	None	None	None	None	I
G/K	0.9136	likely_pathogenic	0.888	pathogenic	-1.195	Destabilizing	0.975	D	0.589	neutral	None	None	None	None	I
G/L	0.7347	likely_pathogenic	0.6919	pathogenic	-0.492	Destabilizing	0.975	D	0.658	neutral	None	None	None	None	I
G/M	0.8001	likely_pathogenic	0.7751	pathogenic	-0.516	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	I
G/N	0.7347	likely_pathogenic	0.67	pathogenic	-0.976	Destabilizing	0.975	D	0.668	neutral	None	None	None	None	I
G/P	0.9851	likely_pathogenic	0.9826	pathogenic	-0.553	Destabilizing	0.987	D	0.687	prob.neutral	None	None	None	None	I
G/Q	0.8032	likely_pathogenic	0.7613	pathogenic	-1.226	Destabilizing	0.975	D	0.689	prob.neutral	None	None	None	None	I
G/R	0.8493	likely_pathogenic	0.82	pathogenic	-0.872	Destabilizing	0.967	D	0.675	neutral	N	0.509209909	None	None	I
G/S	0.1752	likely_benign	0.1509	benign	-1.195	Destabilizing	0.099	N	0.391	neutral	N	0.476539209	None	None	I
G/T	0.4598	ambiguous	0.4224	ambiguous	-1.193	Destabilizing	0.253	N	0.39	neutral	None	None	None	None	I
G/V	0.6355	likely_pathogenic	0.6128	pathogenic	-0.553	Destabilizing	0.967	D	0.701	prob.neutral	D	0.527821143	None	None	I
G/W	0.8453	likely_pathogenic	0.8262	pathogenic	-1.477	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
G/Y	0.8072	likely_pathogenic	0.7989	pathogenic	-1.079	Destabilizing	0.975	D	0.728	prob.delet.	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.