TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18344	55255;55256;55257	chr2:178602372;178602371;178602370	chr2:179467099;179467098;179467097
N2AB	16703	50332;50333;50334	chr2:178602372;178602371;178602370	chr2:179467099;179467098;179467097
N2A	15776	47551;47552;47553	chr2:178602372;178602371;178602370	chr2:179467099;179467098;179467097
N2B	9279	28060;28061;28062	chr2:178602372;178602371;178602370	chr2:179467099;179467098;179467097
Novex-1	9404	28435;28436;28437	chr2:178602372;178602371;178602370	chr2:179467099;179467098;179467097
Novex-2	9471	28636;28637;28638	chr2:178602372;178602371;178602370	chr2:179467099;179467098;179467097
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: Fn3-21
• Domain position: 73
• Structural Position: 103
• Q(SASA): 0.4667
• 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	0.217	N	0.18	0.089	0.283761946502	gnomAD-4.0.0	1.59322E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86162E-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	0.4743	ambiguous	0.5348	ambiguous	-0.741	Destabilizing	0.996	D	0.595	neutral	None	None	None	None	N
K/C	0.6348	likely_pathogenic	0.672	pathogenic	-0.84	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/D	0.709	likely_pathogenic	0.7737	pathogenic	-0.252	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
K/E	0.3043	likely_benign	0.3751	ambiguous	-0.092	Destabilizing	0.989	D	0.484	neutral	N	0.40148106	None	None	N
K/F	0.761	likely_pathogenic	0.8131	pathogenic	-0.207	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
K/G	0.5431	ambiguous	0.6161	pathogenic	-1.148	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
K/H	0.3442	ambiguous	0.372	ambiguous	-1.319	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/I	0.4127	ambiguous	0.4672	ambiguous	0.338	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/L	0.3954	ambiguous	0.4473	ambiguous	0.338	Stabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
K/M	0.2419	likely_benign	0.2787	benign	0.058	Stabilizing	1.0	D	0.735	prob.delet.	N	0.487390678	None	None	N
K/N	0.4229	ambiguous	0.5007	ambiguous	-0.783	Destabilizing	0.998	D	0.653	neutral	N	0.459894645	None	None	N
K/P	0.7009	likely_pathogenic	0.7403	pathogenic	0.008	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
K/Q	0.1868	likely_benign	0.2097	benign	-0.748	Destabilizing	0.997	D	0.646	neutral	N	0.457547773	None	None	N
K/R	0.0929	likely_benign	0.0961	benign	-0.72	Destabilizing	0.217	N	0.18	neutral	N	0.431131963	None	None	N
K/S	0.5136	ambiguous	0.5872	pathogenic	-1.455	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	N
K/T	0.2186	likely_benign	0.2619	benign	-1.073	Destabilizing	0.998	D	0.74	deleterious	N	0.395325878	None	None	N
K/V	0.3868	ambiguous	0.4281	ambiguous	0.008	Stabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
K/W	0.6974	likely_pathogenic	0.7612	pathogenic	-0.082	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
K/Y	0.5856	likely_pathogenic	0.6493	pathogenic	0.195	Stabilizing	1.0	D	0.777	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.