TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25423	76492;76493;76494	chr2:178569865;178569864;178569863	chr2:179434592;179434591;179434590
N2AB	23782	71569;71570;71571	chr2:178569865;178569864;178569863	chr2:179434592;179434591;179434590
N2A	22855	68788;68789;68790	chr2:178569865;178569864;178569863	chr2:179434592;179434591;179434590
N2B	16358	49297;49298;49299	chr2:178569865;178569864;178569863	chr2:179434592;179434591;179434590
Novex-1	16483	49672;49673;49674	chr2:178569865;178569864;178569863	chr2:179434592;179434591;179434590
Novex-2	16550	49873;49874;49875	chr2:178569865;178569864;178569863	chr2:179434592;179434591;179434590
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-73
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.2547
• 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
F/L	rs1034189654	None	0.08	N	0.27	0.2	0.383089235449	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
F/A	0.2732	likely_benign	0.2375	benign	-2.548	Highly Destabilizing	0.103	N	0.362	neutral	None	None	None	None	N
F/C	0.1577	likely_benign	0.1556	benign	-1.26	Destabilizing	0.954	D	0.545	neutral	N	0.471573076	None	None	N
F/D	0.5925	likely_pathogenic	0.5189	ambiguous	-1.855	Destabilizing	0.004	N	0.504	neutral	None	None	None	None	N
F/E	0.6329	likely_pathogenic	0.5728	pathogenic	-1.741	Destabilizing	0.39	N	0.493	neutral	None	None	None	None	N
F/G	0.5784	likely_pathogenic	0.5131	ambiguous	-2.903	Highly Destabilizing	0.345	N	0.441	neutral	None	None	None	None	N
F/H	0.2857	likely_benign	0.2562	benign	-1.143	Destabilizing	0.965	D	0.509	neutral	None	None	None	None	N
F/I	0.1094	likely_benign	0.0985	benign	-1.442	Destabilizing	0.003	N	0.217	neutral	N	0.391245423	None	None	N
F/K	0.5291	ambiguous	0.4772	ambiguous	-1.43	Destabilizing	0.561	D	0.519	neutral	None	None	None	None	N
F/L	0.5254	ambiguous	0.4914	ambiguous	-1.442	Destabilizing	0.08	N	0.27	neutral	N	0.405366727	None	None	N
F/M	0.2761	likely_benign	0.266	benign	-1.06	Destabilizing	0.818	D	0.456	neutral	None	None	None	None	N
F/N	0.2941	likely_benign	0.2649	benign	-1.551	Destabilizing	0.39	N	0.511	neutral	None	None	None	None	N
F/P	0.9802	likely_pathogenic	0.97	pathogenic	-1.81	Destabilizing	0.722	D	0.619	neutral	None	None	None	None	N
F/Q	0.4538	ambiguous	0.4123	ambiguous	-1.666	Destabilizing	0.901	D	0.619	neutral	None	None	None	None	N
F/R	0.436	ambiguous	0.3825	ambiguous	-0.717	Destabilizing	0.901	D	0.621	neutral	None	None	None	None	N
F/S	0.1413	likely_benign	0.12	benign	-2.303	Highly Destabilizing	0.036	N	0.413	neutral	N	0.320459974	None	None	N
F/T	0.1812	likely_benign	0.1706	benign	-2.101	Highly Destabilizing	0.007	N	0.407	neutral	None	None	None	None	N
F/V	0.1127	likely_benign	0.1019	benign	-1.81	Destabilizing	0.005	N	0.255	neutral	N	0.354572547	None	None	N
F/W	0.4366	ambiguous	0.4001	ambiguous	-0.428	Destabilizing	0.991	D	0.479	neutral	None	None	None	None	N
F/Y	0.109	likely_benign	0.103	benign	-0.683	Destabilizing	0.856	D	0.405	neutral	N	0.460356005	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.