TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33012	99259;99260;99261	chr2:178538795;178538794;178538793	chr2:179403522;179403521;179403520
N2AB	31371	94336;94337;94338	chr2:178538795;178538794;178538793	chr2:179403522;179403521;179403520
N2A	30444	91555;91556;91557	chr2:178538795;178538794;178538793	chr2:179403522;179403521;179403520
N2B	23947	72064;72065;72066	chr2:178538795;178538794;178538793	chr2:179403522;179403521;179403520
Novex-1	24072	72439;72440;72441	chr2:178538795;178538794;178538793	chr2:179403522;179403521;179403520
Novex-2	24139	72640;72641;72642	chr2:178538795;178538794;178538793	chr2:179403522;179403521;179403520
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: Fn3-129
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3536
• 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	rs771511344	-0.724	0.716	N	0.495	0.228	0.289098819767	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/E	rs771511344	-0.724	0.716	N	0.495	0.228	0.289098819767	gnomAD-4.0.0	3.42439E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.50064E-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	0.5655	likely_pathogenic	0.5915	pathogenic	-0.444	Destabilizing	0.87	D	0.56	neutral	None	None	None	None	N
K/C	0.8666	likely_pathogenic	0.8889	pathogenic	-0.63	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
K/D	0.8102	likely_pathogenic	0.8392	pathogenic	-0.304	Destabilizing	0.959	D	0.723	prob.delet.	None	None	None	None	N
K/E	0.3953	ambiguous	0.4437	ambiguous	-0.275	Destabilizing	0.716	D	0.495	neutral	N	0.46131601	None	None	N
K/F	0.9645	likely_pathogenic	0.9694	pathogenic	-0.733	Destabilizing	0.994	D	0.749	deleterious	None	None	None	None	N
K/G	0.5499	ambiguous	0.6333	pathogenic	-0.69	Destabilizing	0.959	D	0.651	neutral	None	None	None	None	N
K/H	0.5808	likely_pathogenic	0.6291	pathogenic	-1.182	Destabilizing	0.994	D	0.683	prob.neutral	None	None	None	None	N
K/I	0.7906	likely_pathogenic	0.81	pathogenic	0.145	Stabilizing	0.973	D	0.774	deleterious	N	0.482827222	None	None	N
K/L	0.755	likely_pathogenic	0.7611	pathogenic	0.145	Stabilizing	0.959	D	0.651	neutral	None	None	None	None	N
K/M	0.638	likely_pathogenic	0.6626	pathogenic	0.298	Stabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
K/N	0.7133	likely_pathogenic	0.731	pathogenic	-0.202	Destabilizing	0.946	D	0.695	prob.neutral	N	0.462606876	None	None	N
K/P	0.7061	likely_pathogenic	0.7416	pathogenic	-0.023	Destabilizing	0.979	D	0.713	prob.delet.	None	None	None	None	N
K/Q	0.2791	likely_benign	0.297	benign	-0.532	Destabilizing	0.946	D	0.694	prob.neutral	N	0.508013879	None	None	N
K/R	0.0833	likely_benign	0.0855	benign	-0.258	Destabilizing	0.035	N	0.298	neutral	N	0.48188607	None	None	N
K/S	0.6323	likely_pathogenic	0.6637	pathogenic	-0.832	Destabilizing	0.87	D	0.603	neutral	None	None	None	None	N
K/T	0.4718	ambiguous	0.4966	ambiguous	-0.639	Destabilizing	0.946	D	0.678	prob.neutral	N	0.504202783	None	None	N
K/V	0.7289	likely_pathogenic	0.7342	pathogenic	-0.023	Destabilizing	0.959	D	0.717	prob.delet.	None	None	None	None	N
K/W	0.9044	likely_pathogenic	0.9401	pathogenic	-0.613	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
K/Y	0.8834	likely_pathogenic	0.9149	pathogenic	-0.217	Destabilizing	0.979	D	0.751	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.