TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27395	82408;82409;82410	chr2:178563949;178563948;178563947	chr2:179428676;179428675;179428674
N2AB	25754	77485;77486;77487	chr2:178563949;178563948;178563947	chr2:179428676;179428675;179428674
N2A	24827	74704;74705;74706	chr2:178563949;178563948;178563947	chr2:179428676;179428675;179428674
N2B	18330	55213;55214;55215	chr2:178563949;178563948;178563947	chr2:179428676;179428675;179428674
Novex-1	18455	55588;55589;55590	chr2:178563949;178563948;178563947	chr2:179428676;179428675;179428674
Novex-2	18522	55789;55790;55791	chr2:178563949;178563948;178563947	chr2:179428676;179428675;179428674
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-87
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.889
• 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
L/V	rs1304635139	None	0.166	N	0.305	0.04	0.137902524267	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	1.20726E-04	0	0	0	0	None	0	0	0	0	0
L/V	rs1304635139	None	0.166	N	0.305	0.04	0.137902524267	gnomAD-4.0.0	6.09032E-06	None	None	None	None	I	None	1.04891E-04	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
L/A	0.1123	likely_benign	0.1224	benign	-0.497	Destabilizing	0.002	N	0.155	neutral	None	None	None	None	I
L/C	0.3662	ambiguous	0.3918	ambiguous	-0.501	Destabilizing	0.991	D	0.271	neutral	None	None	None	None	I
L/D	0.4218	ambiguous	0.461	ambiguous	-0.228	Destabilizing	0.39	N	0.383	neutral	None	None	None	None	I
L/E	0.1704	likely_benign	0.1803	benign	-0.337	Destabilizing	0.004	N	0.238	neutral	None	None	None	None	I
L/F	0.1168	likely_benign	0.1358	benign	-0.635	Destabilizing	0.954	D	0.285	neutral	N	0.48788965	None	None	I
L/G	0.2725	likely_benign	0.3028	benign	-0.638	Destabilizing	0.209	N	0.331	neutral	None	None	None	None	I
L/H	0.153	likely_benign	0.1764	benign	-0.025	Destabilizing	0.901	D	0.247	neutral	None	None	None	None	I
L/I	0.0868	likely_benign	0.0926	benign	-0.257	Destabilizing	0.561	D	0.316	neutral	None	None	None	None	I
L/K	0.1313	likely_benign	0.1406	benign	-0.246	Destabilizing	0.017	N	0.216	neutral	None	None	None	None	I
L/M	0.1034	likely_benign	0.1086	benign	-0.312	Destabilizing	0.954	D	0.323	neutral	N	0.510419466	None	None	I
L/N	0.2431	likely_benign	0.265	benign	0.018	Stabilizing	0.561	D	0.394	neutral	None	None	None	None	I
L/P	0.1885	likely_benign	0.2119	benign	-0.304	Destabilizing	0.901	D	0.363	neutral	None	None	None	None	I
L/Q	0.0865	likely_benign	0.0918	benign	-0.238	Destabilizing	0.39	N	0.376	neutral	None	None	None	None	I
L/R	0.1103	likely_benign	0.1264	benign	0.299	Stabilizing	0.39	N	0.386	neutral	None	None	None	None	I
L/S	0.1289	likely_benign	0.1348	benign	-0.386	Destabilizing	0.005	N	0.172	neutral	N	0.432726686	None	None	I
L/T	0.1321	likely_benign	0.1365	benign	-0.391	Destabilizing	0.017	N	0.217	neutral	None	None	None	None	I
L/V	0.0793	likely_benign	0.085	benign	-0.304	Destabilizing	0.166	N	0.305	neutral	N	0.449563008	None	None	I
L/W	0.1947	likely_benign	0.2309	benign	-0.654	Destabilizing	0.987	D	0.28	neutral	N	0.514633207	None	None	I
L/Y	0.2383	likely_benign	0.2741	benign	-0.388	Destabilizing	0.965	D	0.283	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.