TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16971	51136;51137;51138	chr2:178611218;178611217;178611216	chr2:179475945;179475944;179475943
N2AB	15330	46213;46214;46215	chr2:178611218;178611217;178611216	chr2:179475945;179475944;179475943
N2A	14403	43432;43433;43434	chr2:178611218;178611217;178611216	chr2:179475945;179475944;179475943
N2B	7906	23941;23942;23943	chr2:178611218;178611217;178611216	chr2:179475945;179475944;179475943
Novex-1	8031	24316;24317;24318	chr2:178611218;178611217;178611216	chr2:179475945;179475944;179475943
Novex-2	8098	24517;24518;24519	chr2:178611218;178611217;178611216	chr2:179475945;179475944;179475943
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-111
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4979
• 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/N	None	None	1.0	N	0.707	0.186	0.158396225186	gnomAD-4.0.0	1.59383E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86202E-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
K/A	0.3128	likely_benign	0.3297	benign	-0.392	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
K/C	0.6481	likely_pathogenic	0.6612	pathogenic	-0.562	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/D	0.4939	ambiguous	0.5222	ambiguous	0.153	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/E	0.1917	likely_benign	0.2062	benign	0.242	Stabilizing	0.999	D	0.62	neutral	N	0.447743643	None	None	N
K/F	0.7041	likely_pathogenic	0.7512	pathogenic	-0.184	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/G	0.4717	ambiguous	0.4836	ambiguous	-0.723	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/H	0.3114	likely_benign	0.3275	benign	-0.99	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/I	0.2411	likely_benign	0.2835	benign	0.442	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
K/L	0.2866	likely_benign	0.3094	benign	0.442	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/M	0.1586	likely_benign	0.1735	benign	0.237	Stabilizing	1.0	D	0.661	neutral	N	0.481145642	None	None	N
K/N	0.2802	likely_benign	0.3134	benign	-0.275	Destabilizing	1.0	D	0.707	prob.neutral	N	0.445600768	None	None	N
K/P	0.4786	ambiguous	0.4614	ambiguous	0.195	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/Q	0.1462	likely_benign	0.1558	benign	-0.371	Destabilizing	1.0	D	0.681	prob.neutral	N	0.44697698	None	None	N
K/R	0.1026	likely_benign	0.1011	benign	-0.423	Destabilizing	0.999	D	0.581	neutral	N	0.450927833	None	None	N
K/S	0.3538	ambiguous	0.3881	ambiguous	-0.949	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
K/T	0.1234	likely_benign	0.1347	benign	-0.662	Destabilizing	1.0	D	0.707	prob.neutral	N	0.438953191	None	None	N
K/V	0.2409	likely_benign	0.2642	benign	0.195	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/W	0.7782	likely_pathogenic	0.7959	pathogenic	-0.062	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/Y	0.5592	ambiguous	0.5891	pathogenic	0.239	Stabilizing	1.0	D	0.713	prob.delet.	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.