TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4918	14977;14978;14979	chr2:178735694;178735693;178735692	chr2:179600421;179600420;179600419
N2AB	4601	14026;14027;14028	chr2:178735694;178735693;178735692	chr2:179600421;179600420;179600419
N2A	3674	11245;11246;11247	chr2:178735694;178735693;178735692	chr2:179600421;179600420;179600419
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: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-32
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.6411
• 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	rs749179515	0.044	0.97	D	0.669	0.298	0.576674430037	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66003E-04
T/I	rs749179515	0.044	0.97	D	0.669	0.298	0.576674430037	gnomAD-4.0.0	4.77407E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71615E-06	0	3.02462E-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	0.0781	likely_benign	0.0849	benign	-0.607	Destabilizing	0.489	N	0.46	neutral	N	0.510578358	None	None	N
T/C	0.3993	ambiguous	0.4433	ambiguous	-0.426	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
T/D	0.292	likely_benign	0.3435	ambiguous	0.449	Stabilizing	0.956	D	0.616	neutral	None	None	None	None	N
T/E	0.2329	likely_benign	0.2776	benign	0.406	Stabilizing	0.86	D	0.6	neutral	None	None	None	None	N
T/F	0.1708	likely_benign	0.201	benign	-1.085	Destabilizing	0.978	D	0.757	deleterious	None	None	None	None	N
T/G	0.2316	likely_benign	0.2731	benign	-0.76	Destabilizing	0.754	D	0.601	neutral	None	None	None	None	N
T/H	0.1985	likely_benign	0.2258	benign	-0.995	Destabilizing	0.994	D	0.739	prob.delet.	None	None	None	None	N
T/I	0.1251	likely_benign	0.1425	benign	-0.315	Destabilizing	0.97	D	0.669	neutral	D	0.532377904	None	None	N
T/K	0.1548	likely_benign	0.1751	benign	-0.308	Destabilizing	0.698	D	0.572	neutral	N	0.496207717	None	None	N
T/L	0.09	likely_benign	0.1016	benign	-0.315	Destabilizing	0.86	D	0.599	neutral	None	None	None	None	N
T/M	0.0786	likely_benign	0.0827	benign	-0.225	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
T/N	0.1038	likely_benign	0.1171	benign	-0.22	Destabilizing	0.86	D	0.497	neutral	None	None	None	None	N
T/P	0.2563	likely_benign	0.2955	benign	-0.384	Destabilizing	0.97	D	0.668	neutral	D	0.703298797	None	None	N
T/Q	0.1873	likely_benign	0.2099	benign	-0.35	Destabilizing	0.956	D	0.674	neutral	None	None	None	None	N
T/R	0.1263	likely_benign	0.1429	benign	-0.116	Destabilizing	0.032	N	0.28	neutral	N	0.512394281	None	None	N
T/S	0.0989	likely_benign	0.108	benign	-0.496	Destabilizing	0.058	N	0.163	neutral	N	0.503636017	None	None	N
T/V	0.1169	likely_benign	0.1289	benign	-0.384	Destabilizing	0.86	D	0.504	neutral	None	None	None	None	N
T/W	0.4577	ambiguous	0.5182	ambiguous	-1.07	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
T/Y	0.2299	likely_benign	0.2647	benign	-0.779	Destabilizing	0.993	D	0.755	deleterious	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.