TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18294	55105;55106;55107	chr2:178602522;178602521;178602520	chr2:179467249;179467248;179467247
N2AB	16653	50182;50183;50184	chr2:178602522;178602521;178602520	chr2:179467249;179467248;179467247
N2A	15726	47401;47402;47403	chr2:178602522;178602521;178602520	chr2:179467249;179467248;179467247
N2B	9229	27910;27911;27912	chr2:178602522;178602521;178602520	chr2:179467249;179467248;179467247
Novex-1	9354	28285;28286;28287	chr2:178602522;178602521;178602520	chr2:179467249;179467248;179467247
Novex-2	9421	28486;28487;28488	chr2:178602522;178602521;178602520	chr2:179467249;179467248;179467247
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: Fn3-21
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.643
• 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/N	rs770482704	0.157	0.961	N	0.609	0.223	0.173771789658	gnomAD-2.1.1	4.16E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.27E-06	0
K/N	rs770482704	0.157	0.961	N	0.609	0.223	0.173771789658	gnomAD-4.0.0	1.37286E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80289E-06	0	0
K/T	None	None	0.248	N	0.32	0.179	0.218112801441	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.3754	ambiguous	0.2951	benign	-0.068	Destabilizing	0.97	D	0.615	neutral	None	None	None	None	I
K/C	0.6586	likely_pathogenic	0.5867	pathogenic	-0.149	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
K/D	0.6084	likely_pathogenic	0.5616	ambiguous	0.046	Stabilizing	0.092	N	0.311	neutral	None	None	None	None	I
K/E	0.2363	likely_benign	0.1792	benign	0.073	Stabilizing	0.925	D	0.594	neutral	N	0.456603624	None	None	I
K/F	0.7169	likely_pathogenic	0.6353	pathogenic	-0.127	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
K/G	0.4616	ambiguous	0.4037	ambiguous	-0.316	Destabilizing	0.985	D	0.627	neutral	None	None	None	None	I
K/H	0.3354	likely_benign	0.2806	benign	-0.663	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
K/I	0.3077	likely_benign	0.2397	benign	0.518	Stabilizing	0.989	D	0.751	deleterious	N	0.478675194	None	None	I
K/L	0.2986	likely_benign	0.2355	benign	0.518	Stabilizing	0.97	D	0.647	neutral	None	None	None	None	I
K/M	0.1962	likely_benign	0.1576	benign	0.303	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
K/N	0.3664	ambiguous	0.307	benign	0.179	Stabilizing	0.961	D	0.609	neutral	N	0.415413149	None	None	I
K/P	0.8866	likely_pathogenic	0.8383	pathogenic	0.352	Stabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
K/Q	0.1455	likely_benign	0.1184	benign	0.02	Stabilizing	0.994	D	0.654	neutral	N	0.468130126	None	None	I
K/R	0.1122	likely_benign	0.1017	benign	-0.174	Destabilizing	0.98	D	0.593	neutral	N	0.453470105	None	None	I
K/S	0.3859	ambiguous	0.3072	benign	-0.321	Destabilizing	0.942	D	0.569	neutral	None	None	None	None	I
K/T	0.1703	likely_benign	0.13	benign	-0.133	Destabilizing	0.248	N	0.32	neutral	N	0.439980733	None	None	I
K/V	0.2888	likely_benign	0.2291	benign	0.352	Stabilizing	0.991	D	0.661	neutral	None	None	None	None	I
K/W	0.8135	likely_pathogenic	0.7482	pathogenic	-0.109	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
K/Y	0.6049	likely_pathogenic	0.5239	ambiguous	0.219	Stabilizing	0.999	D	0.76	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.