TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6485	19678;19679;19680	chr2:178728371;178728370;178728369	chr2:179593098;179593097;179593096
N2AB	6168	18727;18728;18729	chr2:178728371;178728370;178728369	chr2:179593098;179593097;179593096
N2A	5241	15946;15947;15948	chr2:178728371;178728370;178728369	chr2:179593098;179593097;179593096
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-49
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5747
• 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	0.996	N	0.512	0.181	0.290222751274	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
K/A	0.5308	ambiguous	0.5949	pathogenic	-0.414	Destabilizing	0.997	D	0.576	neutral	None	None	None	None	N
K/C	0.8622	likely_pathogenic	0.9068	pathogenic	-0.406	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/D	0.7325	likely_pathogenic	0.8119	pathogenic	0.052	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/E	0.2153	likely_benign	0.241	benign	0.145	Stabilizing	0.992	D	0.498	neutral	D	0.52376527	None	None	N
K/F	0.9114	likely_pathogenic	0.9342	pathogenic	-0.119	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/G	0.5697	likely_pathogenic	0.6434	pathogenic	-0.758	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
K/H	0.4485	ambiguous	0.5205	ambiguous	-1.039	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
K/I	0.615	likely_pathogenic	0.6507	pathogenic	0.466	Stabilizing	1.0	D	0.693	prob.neutral	N	0.497898462	None	None	N
K/L	0.6308	likely_pathogenic	0.6593	pathogenic	0.466	Stabilizing	1.0	D	0.585	neutral	None	None	None	None	N
K/M	0.4403	ambiguous	0.4531	ambiguous	0.264	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/N	0.6105	likely_pathogenic	0.6983	pathogenic	-0.281	Destabilizing	0.999	D	0.663	neutral	N	0.502444366	None	None	N
K/P	0.9399	likely_pathogenic	0.9555	pathogenic	0.203	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/Q	0.1521	likely_benign	0.1701	benign	-0.346	Destabilizing	0.957	D	0.255	neutral	N	0.475816608	None	None	N
K/R	0.0841	likely_benign	0.0872	benign	-0.49	Destabilizing	0.996	D	0.512	neutral	N	0.440360027	None	None	N
K/S	0.5478	ambiguous	0.6338	pathogenic	-0.901	Destabilizing	0.997	D	0.573	neutral	None	None	None	None	N
K/T	0.315	likely_benign	0.3527	ambiguous	-0.611	Destabilizing	0.999	D	0.668	neutral	N	0.493442363	None	None	N
K/V	0.515	ambiguous	0.5472	ambiguous	0.203	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
K/W	0.855	likely_pathogenic	0.8781	pathogenic	-0.021	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
K/Y	0.8019	likely_pathogenic	0.8453	pathogenic	0.255	Stabilizing	1.0	D	0.669	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.