TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10034	30325;30326;30327	chr2:178704270;178704269;178704268	chr2:179568997;179568996;179568995
N2AB	9717	29374;29375;29376	chr2:178704270;178704269;178704268	chr2:179568997;179568996;179568995
N2A	8790	26593;26594;26595	chr2:178704270;178704269;178704268	chr2:179568997;179568996;179568995
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-85
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.242
• 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/D	None	None	0.007	None	0.453	0.216	0.0716867268079	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.5254	ambiguous	0.4702	ambiguous	-1.35	Destabilizing	0.001	N	0.429	neutral	None	None	None	None	N
H/C	0.1574	likely_benign	0.1373	benign	-0.622	Destabilizing	0.132	N	0.598	neutral	None	None	None	None	N
H/D	0.7212	likely_pathogenic	0.629	pathogenic	-1.094	Destabilizing	0.007	N	0.453	neutral	None	None	None	None	N
H/E	0.6703	likely_pathogenic	0.5776	pathogenic	-0.933	Destabilizing	0.004	N	0.397	neutral	None	None	None	None	N
H/F	0.1731	likely_benign	0.1452	benign	0.286	Stabilizing	None	N	0.285	neutral	None	None	None	None	N
H/G	0.6884	likely_pathogenic	0.6112	pathogenic	-1.777	Destabilizing	0.004	N	0.485	neutral	None	None	None	None	N
H/I	0.2201	likely_benign	0.2009	benign	-0.122	Destabilizing	0.001	N	0.509	neutral	None	None	None	None	N
H/K	0.6032	likely_pathogenic	0.4963	ambiguous	-0.996	Destabilizing	0.002	N	0.437	neutral	None	None	None	None	N
H/L	0.1643	likely_benign	0.1348	benign	-0.122	Destabilizing	0.001	N	0.472	neutral	None	None	None	None	N
H/M	0.4525	ambiguous	0.4256	ambiguous	-0.366	Destabilizing	0.021	N	0.613	neutral	None	None	None	None	N
H/N	0.2424	likely_benign	0.2195	benign	-1.373	Destabilizing	0.007	N	0.359	neutral	None	None	None	None	N
H/P	0.7697	likely_pathogenic	0.6892	pathogenic	-0.515	Destabilizing	0.013	N	0.559	neutral	None	None	None	None	N
H/Q	0.3593	ambiguous	0.2945	benign	-1.003	Destabilizing	0.007	N	0.462	neutral	None	None	None	None	N
H/R	0.3441	ambiguous	0.2483	benign	-1.45	Destabilizing	None	N	0.155	neutral	None	None	None	None	N
H/S	0.4437	ambiguous	0.3888	ambiguous	-1.474	Destabilizing	0.002	N	0.44	neutral	None	None	None	None	N
H/T	0.4232	ambiguous	0.3758	ambiguous	-1.191	Destabilizing	None	N	0.335	neutral	None	None	None	None	N
H/V	0.1605	likely_benign	0.1516	benign	-0.515	Destabilizing	None	N	0.387	neutral	None	None	None	None	N
H/W	0.3059	likely_benign	0.2682	benign	0.752	Stabilizing	0.132	N	0.617	neutral	None	None	None	None	N
H/Y	0.0588	likely_benign	0.0458	benign	0.697	Stabilizing	None	N	0.123	neutral	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.