TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27517	82774;82775;82776	chr2:178563583;178563582;178563581	chr2:179428310;179428309;179428308
N2AB	25876	77851;77852;77853	chr2:178563583;178563582;178563581	chr2:179428310;179428309;179428308
N2A	24949	75070;75071;75072	chr2:178563583;178563582;178563581	chr2:179428310;179428309;179428308
N2B	18452	55579;55580;55581	chr2:178563583;178563582;178563581	chr2:179428310;179428309;179428308
Novex-1	18577	55954;55955;55956	chr2:178563583;178563582;178563581	chr2:179428310;179428309;179428308
Novex-2	18644	56155;56156;56157	chr2:178563583;178563582;178563581	chr2:179428310;179428309;179428308
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-88
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.3752
• 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
T/I	rs1559321324	None	0.032	N	0.257	0.133	0.202949470691	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
T/I	rs1559321324	None	0.032	N	0.257	0.133	0.202949470691	gnomAD-4.0.0	1.36843E-06	None	None	None	None	N	None	0	0	None	0	2.51991E-05	None	0	0	8.99484E-07	0	0
T/N	None	None	0.942	N	0.517	0.253	0.245660935333	gnomAD-4.0.0	2.73685E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59794E-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
T/A	0.1157	likely_benign	0.1142	benign	-0.622	Destabilizing	0.489	N	0.493	neutral	N	0.493313785	None	None	N
T/C	0.4191	ambiguous	0.3926	ambiguous	-0.432	Destabilizing	0.998	D	0.583	neutral	None	None	None	None	N
T/D	0.7974	likely_pathogenic	0.8087	pathogenic	0.169	Stabilizing	0.956	D	0.534	neutral	None	None	None	None	N
T/E	0.6355	likely_pathogenic	0.6647	pathogenic	0.152	Stabilizing	0.956	D	0.511	neutral	None	None	None	None	N
T/F	0.3074	likely_benign	0.316	benign	-0.768	Destabilizing	0.956	D	0.591	neutral	None	None	None	None	N
T/G	0.3167	likely_benign	0.3055	benign	-0.848	Destabilizing	0.754	D	0.503	neutral	None	None	None	None	N
T/H	0.4104	ambiguous	0.4291	ambiguous	-1.05	Destabilizing	0.998	D	0.612	neutral	None	None	None	None	N
T/I	0.1352	likely_benign	0.1278	benign	-0.123	Destabilizing	0.032	N	0.257	neutral	N	0.461241439	None	None	N
T/K	0.4706	ambiguous	0.5153	ambiguous	-0.596	Destabilizing	0.956	D	0.51	neutral	None	None	None	None	N
T/L	0.1054	likely_benign	0.1014	benign	-0.123	Destabilizing	0.559	D	0.494	neutral	None	None	None	None	N
T/M	0.0832	likely_benign	0.0805	benign	-0.04	Destabilizing	0.956	D	0.572	neutral	None	None	None	None	N
T/N	0.189	likely_benign	0.1795	benign	-0.477	Destabilizing	0.942	D	0.517	neutral	N	0.463656102	None	None	N
T/P	0.6649	likely_pathogenic	0.6583	pathogenic	-0.257	Destabilizing	0.97	D	0.567	neutral	N	0.500677987	None	None	N
T/Q	0.3355	likely_benign	0.3494	ambiguous	-0.61	Destabilizing	0.978	D	0.558	neutral	None	None	None	None	N
T/R	0.3854	ambiguous	0.4483	ambiguous	-0.357	Destabilizing	0.956	D	0.569	neutral	None	None	None	None	N
T/S	0.1561	likely_benign	0.158	benign	-0.758	Destabilizing	0.058	N	0.236	neutral	N	0.507840521	None	None	N
T/V	0.1046	likely_benign	0.1021	benign	-0.257	Destabilizing	0.019	N	0.218	neutral	None	None	None	None	N
T/W	0.6744	likely_pathogenic	0.712	pathogenic	-0.737	Destabilizing	0.998	D	0.664	neutral	None	None	None	None	N
T/Y	0.3894	ambiguous	0.3985	ambiguous	-0.493	Destabilizing	0.978	D	0.592	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.