TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17938	54037;54038;54039	chr2:178605483;178605482;178605481	chr2:179470210;179470209;179470208
N2AB	16297	49114;49115;49116	chr2:178605483;178605482;178605481	chr2:179470210;179470209;179470208
N2A	15370	46333;46334;46335	chr2:178605483;178605482;178605481	chr2:179470210;179470209;179470208
N2B	8873	26842;26843;26844	chr2:178605483;178605482;178605481	chr2:179470210;179470209;179470208
Novex-1	8998	27217;27218;27219	chr2:178605483;178605482;178605481	chr2:179470210;179470209;179470208
Novex-2	9065	27418;27419;27420	chr2:178605483;178605482;178605481	chr2:179470210;179470209;179470208
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-18
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.2026
• 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
K/R	None	None	0.006	N	0.335	0.08	0.156986980423	gnomAD-4.0.0	1.59491E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43587E-05	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
K/A	0.7302	likely_pathogenic	0.7125	pathogenic	-1.236	Destabilizing	0.707	D	0.637	neutral	None	None	None	None	N
K/C	0.6986	likely_pathogenic	0.6884	pathogenic	-1.782	Destabilizing	0.995	D	0.785	deleterious	None	None	None	None	N
K/D	0.9722	likely_pathogenic	0.9617	pathogenic	-2.05	Highly Destabilizing	0.894	D	0.744	deleterious	None	None	None	None	N
K/E	0.6587	likely_pathogenic	0.5917	pathogenic	-1.838	Destabilizing	0.477	N	0.637	neutral	N	0.480420912	None	None	N
K/F	0.8698	likely_pathogenic	0.8489	pathogenic	-0.695	Destabilizing	0.985	D	0.798	deleterious	None	None	None	None	N
K/G	0.908	likely_pathogenic	0.8926	pathogenic	-1.622	Destabilizing	0.894	D	0.733	prob.delet.	None	None	None	None	N
K/H	0.5067	ambiguous	0.4723	ambiguous	-1.925	Destabilizing	0.985	D	0.75	deleterious	None	None	None	None	N
K/I	0.5917	likely_pathogenic	0.541	ambiguous	-0.182	Destabilizing	0.928	D	0.809	deleterious	N	0.47180515	None	None	N
K/L	0.5429	ambiguous	0.5152	ambiguous	-0.182	Destabilizing	0.894	D	0.733	prob.delet.	None	None	None	None	N
K/M	0.3323	likely_benign	0.3083	benign	-0.622	Destabilizing	0.995	D	0.737	prob.delet.	None	None	None	None	N
K/N	0.8975	likely_pathogenic	0.8638	pathogenic	-1.834	Destabilizing	0.864	D	0.732	prob.delet.	N	0.493044665	None	None	N
K/P	0.9979	likely_pathogenic	0.9971	pathogenic	-0.51	Destabilizing	0.945	D	0.758	deleterious	None	None	None	None	N
K/Q	0.2935	likely_benign	0.2715	benign	-1.652	Destabilizing	0.864	D	0.736	prob.delet.	N	0.519401522	None	None	N
K/R	0.0972	likely_benign	0.0952	benign	-1.441	Destabilizing	0.006	N	0.335	neutral	N	0.458566493	None	None	N
K/S	0.7938	likely_pathogenic	0.7667	pathogenic	-2.234	Highly Destabilizing	0.707	D	0.661	neutral	None	None	None	None	N
K/T	0.4084	ambiguous	0.3818	ambiguous	-1.816	Destabilizing	0.864	D	0.713	prob.delet.	N	0.471650434	None	None	N
K/V	0.5156	ambiguous	0.4948	ambiguous	-0.51	Destabilizing	0.894	D	0.759	deleterious	None	None	None	None	N
K/W	0.8527	likely_pathogenic	0.8328	pathogenic	-0.847	Destabilizing	0.995	D	0.771	deleterious	None	None	None	None	N
K/Y	0.8067	likely_pathogenic	0.756	pathogenic	-0.442	Destabilizing	0.945	D	0.781	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.