TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6417	19474;19475;19476	chr2:178728677;178728676;178728675	chr2:179593404;179593403;179593402
N2AB	6100	18523;18524;18525	chr2:178728677;178728676;178728675	chr2:179593404;179593403;179593402
N2A	5173	15742;15743;15744	chr2:178728677;178728676;178728675	chr2:179593404;179593403;179593402
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-48
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.467
• 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/E	rs771838033	-0.252	0.939	D	0.493	0.292	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/E	rs771838033	-0.252	0.939	D	0.493	0.292	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
K/E	rs771838033	-0.252	0.939	D	0.493	0.292	None	gnomAD-4.0.0	3.71904E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08644E-06	0	0
K/T	None	None	0.991	N	0.676	0.327	0.444706120422	gnomAD-4.0.0	6.84403E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9963E-07	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	0.4557	ambiguous	0.3878	ambiguous	-1.037	Destabilizing	0.953	D	0.551	neutral	None	None	None	None	N
K/C	0.7438	likely_pathogenic	0.7276	pathogenic	-0.969	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
K/D	0.7987	likely_pathogenic	0.7022	pathogenic	-1.062	Destabilizing	0.993	D	0.692	prob.neutral	None	None	None	None	N
K/E	0.295	likely_benign	0.2005	benign	-0.838	Destabilizing	0.939	D	0.493	neutral	D	0.529208375	None	None	N
K/F	0.8134	likely_pathogenic	0.763	pathogenic	-0.17	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
K/G	0.6512	likely_pathogenic	0.6023	pathogenic	-1.498	Destabilizing	0.993	D	0.683	prob.neutral	None	None	None	None	N
K/H	0.3182	likely_benign	0.2954	benign	-1.487	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
K/I	0.402	ambiguous	0.3209	benign	0.234	Stabilizing	0.991	D	0.737	prob.delet.	N	0.486746421	None	None	N
K/L	0.43	ambiguous	0.3658	ambiguous	0.234	Stabilizing	0.986	D	0.683	prob.neutral	None	None	None	None	N
K/M	0.2598	likely_benign	0.2109	benign	-0.04	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
K/N	0.56	ambiguous	0.4516	ambiguous	-1.368	Destabilizing	0.982	D	0.609	neutral	N	0.498570026	None	None	N
K/P	0.9789	likely_pathogenic	0.9699	pathogenic	-0.164	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
K/Q	0.127	likely_benign	0.11	benign	-1.167	Destabilizing	0.982	D	0.608	neutral	D	0.529152447	None	None	N
K/R	0.0877	likely_benign	0.0875	benign	-1.053	Destabilizing	0.046	N	0.285	neutral	N	0.496906743	None	None	N
K/S	0.4579	ambiguous	0.3889	ambiguous	-1.917	Destabilizing	0.953	D	0.555	neutral	None	None	None	None	N
K/T	0.1783	likely_benign	0.1392	benign	-1.46	Destabilizing	0.991	D	0.676	prob.neutral	N	0.498117464	None	None	N
K/V	0.3732	ambiguous	0.3174	benign	-0.164	Destabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	N
K/W	0.7738	likely_pathogenic	0.7596	pathogenic	-0.148	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
K/Y	0.6674	likely_pathogenic	0.6157	pathogenic	0.093	Stabilizing	0.998	D	0.73	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.