TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30653	92182;92183;92184	chr2:178549765;178549764;178549763	chr2:179414492;179414491;179414490
N2AB	29012	87259;87260;87261	chr2:178549765;178549764;178549763	chr2:179414492;179414491;179414490
N2A	28085	84478;84479;84480	chr2:178549765;178549764;178549763	chr2:179414492;179414491;179414490
N2B	21588	64987;64988;64989	chr2:178549765;178549764;178549763	chr2:179414492;179414491;179414490
Novex-1	21713	65362;65363;65364	chr2:178549765;178549764;178549763	chr2:179414492;179414491;179414490
Novex-2	21780	65563;65564;65565	chr2:178549765;178549764;178549763	chr2:179414492;179414491;179414490
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-111
• Domain position: 35
• Structural Position: 36
• Q(SASA): 0.4448
• 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
T/I	None	None	0.638	N	0.724	0.316	0.487137410055	gnomAD-4.0.0	1.5918E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85941E-06	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
T/A	0.129	likely_benign	0.1454	benign	-0.632	Destabilizing	0.094	N	0.458	neutral	N	0.500503858	None	None	I
T/C	0.4932	ambiguous	0.5252	ambiguous	-0.304	Destabilizing	0.947	D	0.678	prob.neutral	None	None	None	None	I
T/D	0.355	ambiguous	0.3914	ambiguous	-0.244	Destabilizing	0.539	D	0.658	neutral	None	None	None	None	I
T/E	0.3509	ambiguous	0.3917	ambiguous	-0.251	Destabilizing	0.539	D	0.667	neutral	None	None	None	None	I
T/F	0.3615	ambiguous	0.4136	ambiguous	-0.639	Destabilizing	0.826	D	0.749	deleterious	None	None	None	None	I
T/G	0.2578	likely_benign	0.2772	benign	-0.891	Destabilizing	0.25	N	0.581	neutral	None	None	None	None	I
T/H	0.3365	likely_benign	0.3607	ambiguous	-1.188	Destabilizing	0.947	D	0.713	prob.delet.	None	None	None	None	I
T/I	0.3104	likely_benign	0.3053	benign	-0.034	Destabilizing	0.638	D	0.724	prob.delet.	N	0.473854454	None	None	I
T/K	0.3158	likely_benign	0.3549	ambiguous	-0.808	Destabilizing	0.539	D	0.664	neutral	None	None	None	None	I
T/L	0.1434	likely_benign	0.1622	benign	-0.034	Destabilizing	0.399	N	0.619	neutral	None	None	None	None	I
T/M	0.1294	likely_benign	0.1507	benign	0.173	Stabilizing	0.982	D	0.673	neutral	None	None	None	None	I
T/N	0.1499	likely_benign	0.1656	benign	-0.642	Destabilizing	0.468	N	0.639	neutral	N	0.501010837	None	None	I
T/P	0.4944	ambiguous	0.582	pathogenic	-0.201	Destabilizing	0.638	D	0.726	prob.delet.	N	0.505899135	None	None	I
T/Q	0.2989	likely_benign	0.3256	benign	-0.771	Destabilizing	0.7	D	0.717	prob.delet.	None	None	None	None	I
T/R	0.309	likely_benign	0.3484	ambiguous	-0.581	Destabilizing	0.7	D	0.73	prob.delet.	None	None	None	None	I
T/S	0.089	likely_benign	0.0931	benign	-0.856	Destabilizing	0.002	N	0.185	neutral	N	0.469343634	None	None	I
T/V	0.2497	likely_benign	0.249	benign	-0.201	Destabilizing	0.399	N	0.577	neutral	None	None	None	None	I
T/W	0.7268	likely_pathogenic	0.7705	pathogenic	-0.638	Destabilizing	0.982	D	0.759	deleterious	None	None	None	None	I
T/Y	0.3936	ambiguous	0.4382	ambiguous	-0.42	Destabilizing	0.826	D	0.741	deleterious	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.