TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7639	23140;23141;23142	chr2:178721104;178721103;178721102	chr2:179585831;179585830;179585829
N2AB	7322	22189;22190;22191	chr2:178721104;178721103;178721102	chr2:179585831;179585830;179585829
N2A	6395	19408;19409;19410	chr2:178721104;178721103;178721102	chr2:179585831;179585830;179585829
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-61
• Domain position: 32
• Structural Position: 45
• Q(SASA): 0.5199
• Predicted PPI site: I

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/I	rs1413635050	0.756	0.3	N	0.623	0.249	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
K/I	rs1413635050	0.756	0.3	N	0.623	0.249	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/I	rs1413635050	0.756	0.3	N	0.623	0.249	None	gnomAD-4.0.0	1.05378E-05	None	None	None	None	I	None	1.33486E-05	0	None	0	0	None	0	0	1.27181E-05	0	1.60195E-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	0.2183	likely_benign	0.2778	benign	-0.173	Destabilizing	0.73	D	0.525	neutral	None	None	None	None	I
K/C	0.6228	likely_pathogenic	0.6805	pathogenic	-0.182	Destabilizing	0.996	D	0.629	neutral	None	None	None	None	I
K/D	0.3838	ambiguous	0.4837	ambiguous	0.009	Stabilizing	0.004	N	0.235	neutral	None	None	None	None	I
K/E	0.1094	likely_benign	0.1404	benign	0.078	Stabilizing	0.113	N	0.495	neutral	N	0.480089064	None	None	I
K/F	0.6078	likely_pathogenic	0.7097	pathogenic	0.015	Stabilizing	0.959	D	0.619	neutral	None	None	None	None	I
K/G	0.3582	ambiguous	0.4336	ambiguous	-0.484	Destabilizing	0.73	D	0.557	neutral	None	None	None	None	I
K/H	0.1884	likely_benign	0.2277	benign	-0.814	Destabilizing	0.889	D	0.566	neutral	None	None	None	None	I
K/I	0.2277	likely_benign	0.2903	benign	0.602	Stabilizing	0.3	N	0.623	neutral	N	0.492733074	None	None	I
K/L	0.2537	likely_benign	0.3205	benign	0.602	Stabilizing	0.074	N	0.585	neutral	None	None	None	None	I
K/M	0.1626	likely_benign	0.1992	benign	0.309	Stabilizing	0.964	D	0.541	neutral	None	None	None	None	I
K/N	0.2503	likely_benign	0.318	benign	-0.012	Destabilizing	0.672	D	0.467	neutral	N	0.47345388	None	None	I
K/P	0.8001	likely_pathogenic	0.8617	pathogenic	0.374	Stabilizing	0.983	D	0.569	neutral	None	None	None	None	I
K/Q	0.0894	likely_benign	0.1017	benign	-0.087	Destabilizing	0.198	N	0.509	neutral	N	0.490460773	None	None	I
K/R	0.0751	likely_benign	0.0772	benign	-0.358	Destabilizing	0.001	N	0.257	neutral	N	0.455502838	None	None	I
K/S	0.2323	likely_benign	0.3009	benign	-0.518	Destabilizing	0.73	D	0.469	neutral	None	None	None	None	I
K/T	0.0928	likely_benign	0.1165	benign	-0.269	Destabilizing	0.555	D	0.538	neutral	N	0.453193251	None	None	I
K/V	0.2127	likely_benign	0.266	benign	0.374	Stabilizing	0.427	N	0.599	neutral	None	None	None	None	I
K/W	0.582	likely_pathogenic	0.6851	pathogenic	0.046	Stabilizing	0.997	D	0.667	neutral	None	None	None	None	I
K/Y	0.4951	ambiguous	0.5905	pathogenic	0.337	Stabilizing	0.732	D	0.632	neutral	None	None	None	None	I

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.