TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30710	92353;92354;92355	chr2:178549594;178549593;178549592	chr2:179414321;179414320;179414319
N2AB	29069	87430;87431;87432	chr2:178549594;178549593;178549592	chr2:179414321;179414320;179414319
N2A	28142	84649;84650;84651	chr2:178549594;178549593;178549592	chr2:179414321;179414320;179414319
N2B	21645	65158;65159;65160	chr2:178549594;178549593;178549592	chr2:179414321;179414320;179414319
Novex-1	21770	65533;65534;65535	chr2:178549594;178549593;178549592	chr2:179414321;179414320;179414319
Novex-2	21837	65734;65735;65736	chr2:178549594;178549593;178549592	chr2:179414321;179414320;179414319
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-111
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.3111
• 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
P/T	rs2154148331	None	0.986	N	0.722	0.282	0.371531589858	gnomAD-4.0.0	3.18571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72521E-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
P/A	0.0702	likely_benign	0.0788	benign	-0.833	Destabilizing	0.058	N	0.304	neutral	N	0.486982459	None	None	N
P/C	0.4956	ambiguous	0.5772	pathogenic	-0.638	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/D	0.6591	likely_pathogenic	0.712	pathogenic	-0.714	Destabilizing	0.995	D	0.738	deleterious	None	None	None	None	N
P/E	0.4603	ambiguous	0.5102	ambiguous	-0.81	Destabilizing	0.989	D	0.676	prob.neutral	None	None	None	None	N
P/F	0.6784	likely_pathogenic	0.7529	pathogenic	-0.892	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
P/G	0.4255	ambiguous	0.47	ambiguous	-1.022	Destabilizing	0.929	D	0.641	neutral	None	None	None	None	N
P/H	0.3525	ambiguous	0.4149	ambiguous	-0.53	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
P/I	0.4012	ambiguous	0.4617	ambiguous	-0.466	Destabilizing	0.989	D	0.731	deleterious	None	None	None	None	N
P/K	0.4985	ambiguous	0.5496	ambiguous	-0.728	Destabilizing	0.989	D	0.683	prob.neutral	None	None	None	None	N
P/L	0.2152	likely_benign	0.2649	benign	-0.466	Destabilizing	0.986	D	0.626	neutral	N	0.512017385	None	None	N
P/M	0.4241	ambiguous	0.4802	ambiguous	-0.363	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/N	0.5009	ambiguous	0.5547	ambiguous	-0.414	Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	N
P/Q	0.3131	likely_benign	0.3619	ambiguous	-0.693	Destabilizing	0.993	D	0.759	deleterious	N	0.501763943	None	None	N
P/R	0.3462	ambiguous	0.4106	ambiguous	-0.116	Destabilizing	0.993	D	0.739	deleterious	N	0.486786787	None	None	N
P/S	0.1623	likely_benign	0.1836	benign	-0.8	Destabilizing	0.908	D	0.646	neutral	N	0.474163034	None	None	N
P/T	0.131	likely_benign	0.1464	benign	-0.798	Destabilizing	0.986	D	0.722	deleterious	N	0.493659641	None	None	N
P/V	0.2516	likely_benign	0.2926	benign	-0.552	Destabilizing	0.979	D	0.648	neutral	None	None	None	None	N
P/W	0.8385	likely_pathogenic	0.8912	pathogenic	-0.971	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
P/Y	0.6792	likely_pathogenic	0.7479	pathogenic	-0.693	Destabilizing	1.0	D	0.781	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.