TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28200	84823;84824;84825	chr2:178561534;178561533;178561532	chr2:179426261;179426260;179426259
N2AB	26559	79900;79901;79902	chr2:178561534;178561533;178561532	chr2:179426261;179426260;179426259
N2A	25632	77119;77120;77121	chr2:178561534;178561533;178561532	chr2:179426261;179426260;179426259
N2B	19135	57628;57629;57630	chr2:178561534;178561533;178561532	chr2:179426261;179426260;179426259
Novex-1	19260	58003;58004;58005	chr2:178561534;178561533;178561532	chr2:179426261;179426260;179426259
Novex-2	19327	58204;58205;58206	chr2:178561534;178561533;178561532	chr2:179426261;179426260;179426259
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-93
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.6183
• 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/F	rs769081825	-0.52	0.998	N	0.614	0.324	0.558227216974	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
L/F	rs769081825	-0.52	0.998	N	0.614	0.324	0.558227216974	gnomAD-4.0.0	6.84426E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99671E-07	0	0
L/V	None	None	0.979	N	0.569	0.255	0.501308276186	gnomAD-4.0.0	6.84426E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99671E-07	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	0.7466	likely_pathogenic	0.7214	pathogenic	-0.618	Destabilizing	0.968	D	0.568	neutral	None	None	None	None	I
L/C	0.8483	likely_pathogenic	0.8408	pathogenic	-0.763	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
L/D	0.9784	likely_pathogenic	0.9763	pathogenic	-0.097	Destabilizing	0.995	D	0.725	prob.delet.	None	None	None	None	I
L/E	0.8966	likely_pathogenic	0.8845	pathogenic	-0.162	Destabilizing	0.991	D	0.713	prob.delet.	None	None	None	None	I
L/F	0.4186	ambiguous	0.3908	ambiguous	-0.568	Destabilizing	0.998	D	0.614	neutral	N	0.48487791	None	None	I
L/G	0.9197	likely_pathogenic	0.9093	pathogenic	-0.771	Destabilizing	0.991	D	0.712	prob.delet.	None	None	None	None	I
L/H	0.6504	likely_pathogenic	0.6239	pathogenic	0.079	Stabilizing	0.998	D	0.717	prob.delet.	N	0.466013187	None	None	I
L/I	0.1847	likely_benign	0.1792	benign	-0.323	Destabilizing	0.979	D	0.543	neutral	N	0.473103531	None	None	I
L/K	0.7432	likely_pathogenic	0.7162	pathogenic	-0.348	Destabilizing	0.982	D	0.586	neutral	None	None	None	None	I
L/M	0.2438	likely_benign	0.224	benign	-0.607	Destabilizing	0.998	D	0.592	neutral	None	None	None	None	I
L/N	0.8481	likely_pathogenic	0.8273	pathogenic	-0.254	Destabilizing	0.991	D	0.722	prob.delet.	None	None	None	None	I
L/P	0.9433	likely_pathogenic	0.9418	pathogenic	-0.392	Destabilizing	0.998	D	0.725	prob.delet.	N	0.474647241	None	None	I
L/Q	0.5323	ambiguous	0.4855	ambiguous	-0.406	Destabilizing	0.991	D	0.678	prob.neutral	None	None	None	None	I
L/R	0.5604	ambiguous	0.541	ambiguous	0.148	Stabilizing	0.142	N	0.527	neutral	N	0.485771737	None	None	I
L/S	0.8081	likely_pathogenic	0.7848	pathogenic	-0.712	Destabilizing	0.991	D	0.667	neutral	None	None	None	None	I
L/T	0.6845	likely_pathogenic	0.6667	pathogenic	-0.666	Destabilizing	0.991	D	0.619	neutral	None	None	None	None	I
L/V	0.2427	likely_benign	0.2298	benign	-0.392	Destabilizing	0.979	D	0.569	neutral	N	0.513131697	None	None	I
L/W	0.6804	likely_pathogenic	0.6744	pathogenic	-0.578	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
L/Y	0.726	likely_pathogenic	0.7103	pathogenic	-0.351	Destabilizing	0.998	D	0.635	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.