TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15912	47959;47960;47961	chr2:178617351;178617350;178617349	chr2:179482078;179482077;179482076
N2AB	14271	43036;43037;43038	chr2:178617351;178617350;178617349	chr2:179482078;179482077;179482076
N2A	13344	40255;40256;40257	chr2:178617351;178617350;178617349	chr2:179482078;179482077;179482076
N2B	6847	20764;20765;20766	chr2:178617351;178617350;178617349	chr2:179482078;179482077;179482076
Novex-1	6972	21139;21140;21141	chr2:178617351;178617350;178617349	chr2:179482078;179482077;179482076
Novex-2	7039	21340;21341;21342	chr2:178617351;178617350;178617349	chr2:179482078;179482077;179482076
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-3
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.1203
• 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
K/Q	None	None	0.896	N	0.482	0.249	0.171388866994	gnomAD-4.0.0	6.99157E-07	None	None	None	None	I	None	3.13381E-05	0	None	0	0	None	0	0	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
K/A	0.3263	likely_benign	0.3703	ambiguous	0.089	Stabilizing	0.919	D	0.497	neutral	None	None	None	None	I
K/C	0.6596	likely_pathogenic	0.7313	pathogenic	-0.262	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
K/D	0.4631	ambiguous	0.5222	ambiguous	-0.21	Destabilizing	0.988	D	0.524	neutral	None	None	None	None	I
K/E	0.2065	likely_benign	0.218	benign	-0.213	Destabilizing	0.896	D	0.443	neutral	N	0.449707039	None	None	I
K/F	0.6944	likely_pathogenic	0.7636	pathogenic	-0.211	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	I
K/G	0.4269	ambiguous	0.4882	ambiguous	-0.058	Destabilizing	0.959	D	0.525	neutral	None	None	None	None	I
K/H	0.2579	likely_benign	0.2957	benign	-0.187	Destabilizing	0.988	D	0.562	neutral	None	None	None	None	I
K/I	0.3588	ambiguous	0.4305	ambiguous	0.395	Stabilizing	0.984	D	0.643	neutral	N	0.473435515	None	None	I
K/L	0.347	ambiguous	0.4004	ambiguous	0.395	Stabilizing	0.919	D	0.525	neutral	None	None	None	None	I
K/M	0.2534	likely_benign	0.2913	benign	-0.027	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	I
K/N	0.3029	likely_benign	0.3618	ambiguous	0.206	Stabilizing	0.896	D	0.457	neutral	N	0.459475776	None	None	I
K/P	0.7883	likely_pathogenic	0.8261	pathogenic	0.317	Stabilizing	0.996	D	0.557	neutral	None	None	None	None	I
K/Q	0.1273	likely_benign	0.1408	benign	0.074	Stabilizing	0.896	D	0.482	neutral	N	0.47292774	None	None	I
K/R	0.0867	likely_benign	0.087	benign	0.022	Stabilizing	0.011	N	0.103	neutral	N	0.402827448	None	None	I
K/S	0.3586	ambiguous	0.4258	ambiguous	-0.143	Destabilizing	0.919	D	0.421	neutral	None	None	None	None	I
K/T	0.17	likely_benign	0.1952	benign	-0.025	Destabilizing	0.946	D	0.506	neutral	N	0.387258798	None	None	I
K/V	0.3177	likely_benign	0.3719	ambiguous	0.317	Stabilizing	0.988	D	0.544	neutral	None	None	None	None	I
K/W	0.7356	likely_pathogenic	0.7876	pathogenic	-0.325	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
K/Y	0.559	ambiguous	0.615	pathogenic	0.032	Stabilizing	0.996	D	0.637	neutral	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.