TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28003	84232;84233;84234	chr2:178562125;178562124;178562123	chr2:179426852;179426851;179426850
N2AB	26362	79309;79310;79311	chr2:178562125;178562124;178562123	chr2:179426852;179426851;179426850
N2A	25435	76528;76529;76530	chr2:178562125;178562124;178562123	chr2:179426852;179426851;179426850
N2B	18938	57037;57038;57039	chr2:178562125;178562124;178562123	chr2:179426852;179426851;179426850
Novex-1	19063	57412;57413;57414	chr2:178562125;178562124;178562123	chr2:179426852;179426851;179426850
Novex-2	19130	57613;57614;57615	chr2:178562125;178562124;178562123	chr2:179426852;179426851;179426850
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-142
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.231
• 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
L/V	None	None	0.999	D	0.474	0.416	0.470237251169	gnomAD-4.0.0	1.36896E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99649E-07	0	1.65733E-05

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
L/A	0.8602	likely_pathogenic	0.8582	pathogenic	-2.062	Highly Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
L/C	0.8904	likely_pathogenic	0.8898	pathogenic	-1.45	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
L/D	0.9957	likely_pathogenic	0.9963	pathogenic	-1.551	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/E	0.9666	likely_pathogenic	0.9722	pathogenic	-1.394	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/F	0.483	ambiguous	0.4455	ambiguous	-1.17	Destabilizing	1.0	D	0.697	prob.neutral	D	0.525799903	None	None	N
L/G	0.9734	likely_pathogenic	0.9748	pathogenic	-2.543	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/H	0.932	likely_pathogenic	0.9454	pathogenic	-1.763	Destabilizing	1.0	D	0.805	deleterious	D	0.556274422	None	None	N
L/I	0.1279	likely_benign	0.1149	benign	-0.728	Destabilizing	0.999	D	0.477	neutral	N	0.486888233	None	None	N
L/K	0.9342	likely_pathogenic	0.9498	pathogenic	-1.529	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/M	0.2736	likely_benign	0.2535	benign	-0.707	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
L/N	0.9782	likely_pathogenic	0.9813	pathogenic	-1.649	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/P	0.8944	likely_pathogenic	0.903	pathogenic	-1.147	Destabilizing	1.0	D	0.825	deleterious	D	0.556020932	None	None	N
L/Q	0.872	likely_pathogenic	0.8975	pathogenic	-1.581	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/R	0.8869	likely_pathogenic	0.9188	pathogenic	-1.187	Destabilizing	1.0	D	0.819	deleterious	D	0.533308322	None	None	N
L/S	0.958	likely_pathogenic	0.9607	pathogenic	-2.404	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/T	0.8617	likely_pathogenic	0.8672	pathogenic	-2.094	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
L/V	0.1469	likely_benign	0.1419	benign	-1.147	Destabilizing	0.999	D	0.474	neutral	D	0.525944358	None	None	N
L/W	0.7867	likely_pathogenic	0.7893	pathogenic	-1.369	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
L/Y	0.8864	likely_pathogenic	0.8873	pathogenic	-1.105	Destabilizing	1.0	D	0.815	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.