TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25970	78133;78134;78135	chr2:178568224;178568223;178568222	chr2:179432951;179432950;179432949
N2AB	24329	73210;73211;73212	chr2:178568224;178568223;178568222	chr2:179432951;179432950;179432949
N2A	23402	70429;70430;70431	chr2:178568224;178568223;178568222	chr2:179432951;179432950;179432949
N2B	16905	50938;50939;50940	chr2:178568224;178568223;178568222	chr2:179432951;179432950;179432949
Novex-1	17030	51313;51314;51315	chr2:178568224;178568223;178568222	chr2:179432951;179432950;179432949
Novex-2	17097	51514;51515;51516	chr2:178568224;178568223;178568222	chr2:179432951;179432950;179432949
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-76
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.5947
• 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
R/K	rs1356017017	0.281	0.873	N	0.436	0.201	0.342865806769	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
R/K	rs1356017017	0.281	0.873	N	0.436	0.201	0.342865806769	gnomAD-4.0.0	1.5917E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85945E-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
R/A	0.9817	likely_pathogenic	0.9822	pathogenic	0.128	Stabilizing	0.916	D	0.543	neutral	None	None	None	None	I
R/C	0.8774	likely_pathogenic	0.8414	pathogenic	-0.029	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	I
R/D	0.9936	likely_pathogenic	0.9946	pathogenic	-0.188	Destabilizing	0.996	D	0.573	neutral	None	None	None	None	I
R/E	0.9759	likely_pathogenic	0.9781	pathogenic	-0.114	Destabilizing	0.957	D	0.493	neutral	None	None	None	None	I
R/F	0.9885	likely_pathogenic	0.9891	pathogenic	-0.112	Destabilizing	0.975	D	0.601	neutral	None	None	None	None	I
R/G	0.9706	likely_pathogenic	0.972	pathogenic	-0.061	Destabilizing	0.983	D	0.479	neutral	N	0.458243917	None	None	I
R/H	0.6987	likely_pathogenic	0.6765	pathogenic	-0.798	Destabilizing	0.999	D	0.459	neutral	None	None	None	None	I
R/I	0.9341	likely_pathogenic	0.9397	pathogenic	0.59	Stabilizing	0.935	D	0.535	neutral	N	0.515267925	None	None	I
R/K	0.5501	ambiguous	0.4931	ambiguous	0.07	Stabilizing	0.873	D	0.436	neutral	N	0.474920026	None	None	I
R/L	0.9278	likely_pathogenic	0.929	pathogenic	0.59	Stabilizing	0.033	N	0.523	neutral	None	None	None	None	I
R/M	0.969	likely_pathogenic	0.9672	pathogenic	0.031	Stabilizing	0.975	D	0.503	neutral	None	None	None	None	I
R/N	0.986	likely_pathogenic	0.9879	pathogenic	0.189	Stabilizing	0.996	D	0.477	neutral	None	None	None	None	I
R/P	0.9792	likely_pathogenic	0.98	pathogenic	0.457	Stabilizing	0.996	D	0.566	neutral	None	None	None	None	I
R/Q	0.7002	likely_pathogenic	0.667	pathogenic	0.173	Stabilizing	0.996	D	0.484	neutral	None	None	None	None	I
R/S	0.9849	likely_pathogenic	0.987	pathogenic	-0.007	Destabilizing	0.983	D	0.496	neutral	N	0.489273403	None	None	I
R/T	0.9716	likely_pathogenic	0.9774	pathogenic	0.199	Stabilizing	0.892	D	0.509	neutral	N	0.508685883	None	None	I
R/V	0.9613	likely_pathogenic	0.9644	pathogenic	0.457	Stabilizing	0.845	D	0.545	neutral	None	None	None	None	I
R/W	0.8958	likely_pathogenic	0.8792	pathogenic	-0.274	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
R/Y	0.9548	likely_pathogenic	0.9505	pathogenic	0.152	Stabilizing	0.987	D	0.575	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.