TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14460	43603;43604;43605	chr2:178632628;178632627;178632626	chr2:179497355;179497354;179497353
N2AB	12819	38680;38681;38682	chr2:178632628;178632627;178632626	chr2:179497355;179497354;179497353
N2A	11892	35899;35900;35901	chr2:178632628;178632627;178632626	chr2:179497355;179497354;179497353
N2B	5395	16408;16409;16410	chr2:178632628;178632627;178632626	chr2:179497355;179497354;179497353
Novex-1	5520	16783;16784;16785	chr2:178632628;178632627;178632626	chr2:179497355;179497354;179497353
Novex-2	5587	16984;16985;16986	chr2:178632628;178632627;178632626	chr2:179497355;179497354;179497353
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-95
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.293
• 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	rs1452796827	0.166	0.996	N	0.441	0.317	0.444907495582	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
T/I	rs1452796827	0.166	0.996	N	0.441	0.317	0.444907495582	gnomAD-4.0.0	5.47451E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19673E-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	0.1316	likely_benign	0.1188	benign	-0.858	Destabilizing	0.826	D	0.34	neutral	N	0.503435424	None	None	N
T/C	0.6237	likely_pathogenic	0.5433	ambiguous	-0.654	Destabilizing	0.999	D	0.457	neutral	None	None	None	None	N
T/D	0.5696	likely_pathogenic	0.5323	ambiguous	-1.203	Destabilizing	0.939	D	0.387	neutral	None	None	None	None	N
T/E	0.4147	ambiguous	0.3862	ambiguous	-1.14	Destabilizing	0.759	D	0.401	neutral	None	None	None	None	N
T/F	0.3603	ambiguous	0.3246	benign	-0.641	Destabilizing	0.997	D	0.56	neutral	None	None	None	None	N
T/G	0.3638	ambiguous	0.3271	benign	-1.188	Destabilizing	0.969	D	0.518	neutral	None	None	None	None	N
T/H	0.3783	ambiguous	0.3201	benign	-1.466	Destabilizing	0.991	D	0.543	neutral	None	None	None	None	N
T/I	0.2544	likely_benign	0.2484	benign	-0.041	Destabilizing	0.996	D	0.441	neutral	N	0.510725339	None	None	N
T/K	0.1692	likely_benign	0.1535	benign	-1.042	Destabilizing	0.079	N	0.178	neutral	None	None	None	None	N
T/L	0.1286	likely_benign	0.1161	benign	-0.041	Destabilizing	0.939	D	0.397	neutral	None	None	None	None	N
T/M	0.1129	likely_benign	0.0954	benign	0.233	Stabilizing	0.997	D	0.458	neutral	None	None	None	None	N
T/N	0.1624	likely_benign	0.1509	benign	-1.243	Destabilizing	0.959	D	0.343	neutral	N	0.498571394	None	None	N
T/P	0.1792	likely_benign	0.1638	benign	-0.28	Destabilizing	0.996	D	0.427	neutral	D	0.561545739	None	None	N
T/Q	0.2404	likely_benign	0.2174	benign	-1.308	Destabilizing	0.373	N	0.29	neutral	None	None	None	None	N
T/R	0.1319	likely_benign	0.1178	benign	-0.869	Destabilizing	0.046	N	0.228	neutral	None	None	None	None	N
T/S	0.1776	likely_benign	0.1584	benign	-1.399	Destabilizing	0.826	D	0.366	neutral	N	0.506260971	None	None	N
T/V	0.212	likely_benign	0.2031	benign	-0.28	Destabilizing	0.969	D	0.358	neutral	None	None	None	None	N
T/W	0.7059	likely_pathogenic	0.6397	pathogenic	-0.687	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
T/Y	0.417	ambiguous	0.3695	ambiguous	-0.428	Destabilizing	0.997	D	0.56	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.