TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14661	44206;44207;44208	chr2:178631067;178631066;178631065	chr2:179495794;179495793;179495792
N2AB	13020	39283;39284;39285	chr2:178631067;178631066;178631065	chr2:179495794;179495793;179495792
N2A	12093	36502;36503;36504	chr2:178631067;178631066;178631065	chr2:179495794;179495793;179495792
N2B	5596	17011;17012;17013	chr2:178631067;178631066;178631065	chr2:179495794;179495793;179495792
Novex-1	5721	17386;17387;17388	chr2:178631067;178631066;178631065	chr2:179495794;179495793;179495792
Novex-2	5788	17587;17588;17589	chr2:178631067;178631066;178631065	chr2:179495794;179495793;179495792
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-97
• Domain position: 76
• Structural Position: 161
• Q(SASA): 0.6112
• 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
T/I	rs370339661	-0.02	0.997	N	0.505	0.425	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
T/I	rs370339661	-0.02	0.997	N	0.505	0.425	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs370339661	-0.02	0.997	N	0.505	0.425	None	gnomAD-4.0.0	6.57626E-06	None	None	None	None	N	None	2.41371E-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
T/A	0.1382	likely_benign	0.1131	benign	-0.268	Destabilizing	0.9	D	0.493	neutral	N	0.45258781	None	None	N
T/C	0.7691	likely_pathogenic	0.7573	pathogenic	-0.19	Destabilizing	1.0	D	0.513	neutral	None	None	None	None	N
T/D	0.4888	ambiguous	0.4453	ambiguous	0.097	Stabilizing	0.995	D	0.467	neutral	None	None	None	None	N
T/E	0.3958	ambiguous	0.3502	ambiguous	0.012	Stabilizing	0.995	D	0.481	neutral	None	None	None	None	N
T/F	0.4406	ambiguous	0.4195	ambiguous	-0.826	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
T/G	0.3986	ambiguous	0.3456	ambiguous	-0.377	Destabilizing	0.983	D	0.497	neutral	None	None	None	None	N
T/H	0.4472	ambiguous	0.4306	ambiguous	-0.651	Destabilizing	1.0	D	0.56	neutral	None	None	None	None	N
T/I	0.3548	ambiguous	0.3304	benign	-0.103	Destabilizing	0.997	D	0.505	neutral	N	0.506045346	None	None	N
T/K	0.2448	likely_benign	0.2247	benign	-0.288	Destabilizing	0.994	D	0.47	neutral	N	0.452106788	None	None	N
T/L	0.2123	likely_benign	0.1875	benign	-0.103	Destabilizing	0.992	D	0.506	neutral	None	None	None	None	N
T/M	0.1392	likely_benign	0.1269	benign	0.059	Stabilizing	1.0	D	0.505	neutral	None	None	None	None	N
T/N	0.1847	likely_benign	0.1561	benign	-0.048	Destabilizing	0.995	D	0.457	neutral	None	None	None	None	N
T/P	0.2431	likely_benign	0.2341	benign	-0.131	Destabilizing	0.997	D	0.499	neutral	D	0.548754144	None	None	N
T/Q	0.3495	ambiguous	0.3244	benign	-0.29	Destabilizing	0.998	D	0.486	neutral	None	None	None	None	N
T/R	0.2022	likely_benign	0.1941	benign	0.003	Stabilizing	0.997	D	0.493	neutral	N	0.491651796	None	None	N
T/S	0.174	likely_benign	0.142	benign	-0.238	Destabilizing	0.63	D	0.259	neutral	N	0.440780413	None	None	N
T/V	0.3313	likely_benign	0.2914	benign	-0.131	Destabilizing	0.992	D	0.477	neutral	None	None	None	None	N
T/W	0.7729	likely_pathogenic	0.7823	pathogenic	-0.858	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	N
T/Y	0.5125	ambiguous	0.5112	ambiguous	-0.558	Destabilizing	0.999	D	0.55	neutral	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.