TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26949	81070;81071;81072	chr2:178565287;178565286;178565285	chr2:179430014;179430013;179430012
N2AB	25308	76147;76148;76149	chr2:178565287;178565286;178565285	chr2:179430014;179430013;179430012
N2A	24381	73366;73367;73368	chr2:178565287;178565286;178565285	chr2:179430014;179430013;179430012
N2B	17884	53875;53876;53877	chr2:178565287;178565286;178565285	chr2:179430014;179430013;179430012
Novex-1	18009	54250;54251;54252	chr2:178565287;178565286;178565285	chr2:179430014;179430013;179430012
Novex-2	18076	54451;54452;54453	chr2:178565287;178565286;178565285	chr2:179430014;179430013;179430012
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: Ig-139
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.1871
• Predicted PPI site: N

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/I	rs775669416	0.326	0.97	D	0.759	0.522	0.705868728084	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
K/I	rs775669416	0.326	0.97	D	0.759	0.522	0.705868728084	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/I	rs775669416	0.326	0.97	D	0.759	0.522	0.705868728084	gnomAD-4.0.0	3.04492E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61481E-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	0.2665	likely_benign	0.2287	benign	-0.526	Destabilizing	0.86	D	0.557	neutral	None	None	None	None	N
K/C	0.496	ambiguous	0.4486	ambiguous	-0.59	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
K/D	0.43	ambiguous	0.3777	ambiguous	0.071	Stabilizing	0.754	D	0.595	neutral	None	None	None	None	N
K/E	0.1518	likely_benign	0.1284	benign	0.137	Stabilizing	0.014	N	0.339	neutral	N	0.514684427	None	None	N
K/F	0.5331	ambiguous	0.4677	ambiguous	-0.508	Destabilizing	0.978	D	0.76	deleterious	None	None	None	None	N
K/G	0.4148	ambiguous	0.3569	ambiguous	-0.829	Destabilizing	0.86	D	0.639	neutral	None	None	None	None	N
K/H	0.1906	likely_benign	0.1758	benign	-1.227	Destabilizing	0.043	N	0.403	neutral	None	None	None	None	N
K/I	0.1639	likely_benign	0.1497	benign	0.228	Stabilizing	0.97	D	0.759	deleterious	D	0.52882716	None	None	N
K/L	0.2205	likely_benign	0.1943	benign	0.228	Stabilizing	0.956	D	0.669	neutral	None	None	None	None	N
K/M	0.1361	likely_benign	0.1238	benign	0.23	Stabilizing	0.998	D	0.674	neutral	None	None	None	None	N
K/N	0.2354	likely_benign	0.2079	benign	-0.2	Destabilizing	0.822	D	0.555	neutral	N	0.508355888	None	None	N
K/P	0.659	likely_pathogenic	0.6271	pathogenic	0.006	Stabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
K/Q	0.1065	likely_benign	0.0959	benign	-0.403	Destabilizing	0.89	D	0.579	neutral	N	0.514569784	None	None	N
K/R	0.0772	likely_benign	0.0749	benign	-0.382	Destabilizing	0.822	D	0.525	neutral	D	0.522727907	None	None	N
K/S	0.2736	likely_benign	0.239	benign	-0.916	Destabilizing	0.86	D	0.523	neutral	None	None	None	None	N
K/T	0.1067	likely_benign	0.0974	benign	-0.66	Destabilizing	0.942	D	0.647	neutral	N	0.509086606	None	None	N
K/V	0.1735	likely_benign	0.1527	benign	0.006	Stabilizing	0.978	D	0.702	prob.neutral	None	None	None	None	N
K/W	0.6041	likely_pathogenic	0.5523	ambiguous	-0.348	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
K/Y	0.4047	ambiguous	0.3534	ambiguous	-0.02	Destabilizing	0.956	D	0.736	prob.delet.	None	None	None	None	N

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.