TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28471	85636;85637;85638	chr2:178560721;178560720;178560719	chr2:179425448;179425447;179425446
N2AB	26830	80713;80714;80715	chr2:178560721;178560720;178560719	chr2:179425448;179425447;179425446
N2A	25903	77932;77933;77934	chr2:178560721;178560720;178560719	chr2:179425448;179425447;179425446
N2B	19406	58441;58442;58443	chr2:178560721;178560720;178560719	chr2:179425448;179425447;179425446
Novex-1	19531	58816;58817;58818	chr2:178560721;178560720;178560719	chr2:179425448;179425447;179425446
Novex-2	19598	59017;59018;59019	chr2:178560721;178560720;178560719	chr2:179425448;179425447;179425446
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-95
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.2354
• 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
S/A	rs1185011450	-0.955	0.061	N	0.179	0.113	0.226586394389	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
S/A	rs1185011450	-0.955	0.061	N	0.179	0.113	0.226586394389	gnomAD-4.0.0	1.59153E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85816E-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
S/A	0.0929	likely_benign	0.0869	benign	-1.085	Destabilizing	0.061	N	0.179	neutral	N	0.496359664	None	None	N
S/C	0.0973	likely_benign	0.0973	benign	-0.755	Destabilizing	0.077	N	0.36	neutral	N	0.491583997	None	None	N
S/D	0.5042	ambiguous	0.4846	ambiguous	-0.41	Destabilizing	0.884	D	0.427	neutral	None	None	None	None	N
S/E	0.5203	ambiguous	0.5065	ambiguous	-0.348	Destabilizing	0.939	D	0.432	neutral	None	None	None	None	N
S/F	0.1351	likely_benign	0.124	benign	-1.234	Destabilizing	0.996	D	0.576	neutral	N	0.519474394	None	None	N
S/G	0.1518	likely_benign	0.1446	benign	-1.371	Destabilizing	0.863	D	0.357	neutral	None	None	None	None	N
S/H	0.2343	likely_benign	0.2342	benign	-1.718	Destabilizing	0.991	D	0.569	neutral	None	None	None	None	N
S/I	0.1362	likely_benign	0.1307	benign	-0.407	Destabilizing	0.939	D	0.569	neutral	None	None	None	None	N
S/K	0.5268	ambiguous	0.5279	ambiguous	-0.466	Destabilizing	0.939	D	0.431	neutral	None	None	None	None	N
S/L	0.0813	likely_benign	0.0813	benign	-0.407	Destabilizing	0.939	D	0.481	neutral	None	None	None	None	N
S/M	0.189	likely_benign	0.1829	benign	-0.222	Destabilizing	0.997	D	0.569	neutral	None	None	None	None	N
S/N	0.168	likely_benign	0.1633	benign	-0.641	Destabilizing	0.17	N	0.34	neutral	None	None	None	None	N
S/P	0.9043	likely_pathogenic	0.9214	pathogenic	-0.601	Destabilizing	0.988	D	0.55	neutral	D	0.5308307	None	None	N
S/Q	0.39	ambiguous	0.3789	ambiguous	-0.722	Destabilizing	0.991	D	0.532	neutral	None	None	None	None	N
S/R	0.4055	ambiguous	0.3923	ambiguous	-0.484	Destabilizing	0.991	D	0.551	neutral	None	None	None	None	N
S/T	0.0816	likely_benign	0.0812	benign	-0.651	Destabilizing	0.061	N	0.175	neutral	N	0.466247401	None	None	N
S/V	0.1564	likely_benign	0.1534	benign	-0.601	Destabilizing	0.939	D	0.483	neutral	None	None	None	None	N
S/W	0.2365	likely_benign	0.2195	benign	-1.177	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
S/Y	0.132	likely_benign	0.1279	benign	-0.88	Destabilizing	0.996	D	0.598	neutral	N	0.512726445	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.