TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18427	55504;55505;55506	chr2:178601905;178601904;178601903	chr2:179466632;179466631;179466630
N2AB	16786	50581;50582;50583	chr2:178601905;178601904;178601903	chr2:179466632;179466631;179466630
N2A	15859	47800;47801;47802	chr2:178601905;178601904;178601903	chr2:179466632;179466631;179466630
N2B	9362	28309;28310;28311	chr2:178601905;178601904;178601903	chr2:179466632;179466631;179466630
Novex-1	9487	28684;28685;28686	chr2:178601905;178601904;178601903	chr2:179466632;179466631;179466630
Novex-2	9554	28885;28886;28887	chr2:178601905;178601904;178601903	chr2:179466632;179466631;179466630
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-115
• Domain position: 46
• Structural Position: 66
• Q(SASA): 0.6452
• 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
H/R	None	None	0.997	N	0.656	0.313	0.151104730317	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
H/A	0.3401	ambiguous	0.3308	benign	-1.455	Destabilizing	0.997	D	0.669	neutral	None	None	None	None	N
H/C	0.2042	likely_benign	0.187	benign	-0.721	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
H/D	0.3096	likely_benign	0.3141	benign	-1.228	Destabilizing	0.997	D	0.645	neutral	N	0.505077069	None	None	N
H/E	0.4348	ambiguous	0.4218	ambiguous	-1.063	Destabilizing	0.997	D	0.667	neutral	None	None	None	None	N
H/F	0.3417	ambiguous	0.3312	benign	0.16	Stabilizing	0.999	D	0.652	neutral	None	None	None	None	N
H/G	0.3832	ambiguous	0.3959	ambiguous	-1.882	Destabilizing	0.997	D	0.669	neutral	None	None	None	None	N
H/I	0.3976	ambiguous	0.3689	ambiguous	-0.218	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
H/K	0.4378	ambiguous	0.4412	ambiguous	-0.98	Destabilizing	0.997	D	0.645	neutral	None	None	None	None	N
H/L	0.1889	likely_benign	0.1961	benign	-0.218	Destabilizing	0.999	D	0.649	neutral	N	0.502303336	None	None	N
H/M	0.4934	ambiguous	0.4683	ambiguous	-0.417	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
H/N	0.1154	likely_benign	0.1108	benign	-1.4	Destabilizing	0.997	D	0.685	prob.neutral	N	0.455728113	None	None	N
H/P	0.2483	likely_benign	0.2979	benign	-0.616	Destabilizing	0.999	D	0.694	prob.neutral	N	0.475543596	None	None	N
H/Q	0.2673	likely_benign	0.2616	benign	-1.031	Destabilizing	0.999	D	0.642	neutral	N	0.504730353	None	None	N
H/R	0.234	likely_benign	0.2538	benign	-1.346	Destabilizing	0.997	D	0.656	neutral	N	0.455474623	None	None	N
H/S	0.2482	likely_benign	0.2357	benign	-1.531	Destabilizing	0.997	D	0.673	neutral	None	None	None	None	N
H/T	0.3217	likely_benign	0.2987	benign	-1.245	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
H/V	0.3444	ambiguous	0.3282	benign	-0.616	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
H/W	0.4506	ambiguous	0.4486	ambiguous	0.614	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
H/Y	0.133	likely_benign	0.1344	benign	0.557	Stabilizing	0.997	D	0.647	neutral	N	0.454967644	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.