TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7366	22321;22322;22323	chr2:178722803;178722802;178722801	chr2:179587530;179587529;179587528
N2AB	7049	21370;21371;21372	chr2:178722803;178722802;178722801	chr2:179587530;179587529;179587528
N2A	6122	18589;18590;18591	chr2:178722803;178722802;178722801	chr2:179587530;179587529;179587528
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-58
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.2033
• 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/S	None	None	0.159	N	0.187	0.062	0.0611884634855	gnomAD-4.0.0	1.36875E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99603E-07	0	1.65788E-05

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	0.0778	likely_benign	0.1081	benign	-0.57	Destabilizing	0.704	D	0.358	neutral	N	0.4220959	None	None	N
T/C	0.541	ambiguous	0.7071	pathogenic	-0.34	Destabilizing	0.999	D	0.294	neutral	None	None	None	None	N
T/D	0.4127	ambiguous	0.6616	pathogenic	0.154	Stabilizing	0.046	N	0.274	neutral	None	None	None	None	N
T/E	0.4167	ambiguous	0.6491	pathogenic	0.141	Stabilizing	0.884	D	0.316	neutral	None	None	None	None	N
T/F	0.2809	likely_benign	0.4633	ambiguous	-0.732	Destabilizing	0.997	D	0.374	neutral	None	None	None	None	N
T/G	0.1721	likely_benign	0.2424	benign	-0.796	Destabilizing	0.02	N	0.226	neutral	None	None	None	None	N
T/H	0.2973	likely_benign	0.4609	ambiguous	-1.025	Destabilizing	0.999	D	0.357	neutral	None	None	None	None	N
T/I	0.226	likely_benign	0.4073	ambiguous	-0.071	Destabilizing	0.988	D	0.317	neutral	N	0.464617313	None	None	N
T/K	0.2637	likely_benign	0.4232	ambiguous	-0.587	Destabilizing	0.939	D	0.308	neutral	None	None	None	None	N
T/L	0.1052	likely_benign	0.1568	benign	-0.071	Destabilizing	0.969	D	0.301	neutral	None	None	None	None	N
T/M	0.1005	likely_benign	0.1341	benign	-0.015	Destabilizing	0.999	D	0.282	neutral	None	None	None	None	N
T/N	0.1204	likely_benign	0.1883	benign	-0.461	Destabilizing	0.92	D	0.375	neutral	N	0.403547425	None	None	N
T/P	0.2333	likely_benign	0.3847	ambiguous	-0.206	Destabilizing	0.988	D	0.311	neutral	N	0.454130961	None	None	N
T/Q	0.2835	likely_benign	0.4407	ambiguous	-0.561	Destabilizing	0.991	D	0.319	neutral	None	None	None	None	N
T/R	0.2363	likely_benign	0.4035	ambiguous	-0.382	Destabilizing	0.991	D	0.321	neutral	None	None	None	None	N
T/S	0.0844	likely_benign	0.1128	benign	-0.708	Destabilizing	0.159	N	0.187	neutral	N	0.334068697	None	None	N
T/V	0.1677	likely_benign	0.2831	benign	-0.206	Destabilizing	0.969	D	0.364	neutral	None	None	None	None	N
T/W	0.7067	likely_pathogenic	0.8691	pathogenic	-0.746	Destabilizing	0.999	D	0.425	neutral	None	None	None	None	N
T/Y	0.3996	ambiguous	0.6039	pathogenic	-0.493	Destabilizing	0.997	D	0.374	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.