TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32352	97279;97280;97281	chr2:178542800;178542799;178542798	chr2:179407527;179407526;179407525
N2AB	30711	92356;92357;92358	chr2:178542800;178542799;178542798	chr2:179407527;179407526;179407525
N2A	29784	89575;89576;89577	chr2:178542800;178542799;178542798	chr2:179407527;179407526;179407525
N2B	23287	70084;70085;70086	chr2:178542800;178542799;178542798	chr2:179407527;179407526;179407525
Novex-1	23412	70459;70460;70461	chr2:178542800;178542799;178542798	chr2:179407527;179407526;179407525
Novex-2	23479	70660;70661;70662	chr2:178542800;178542799;178542798	chr2:179407527;179407526;179407525
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Ig-154
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.2246
• 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
R/C	rs753874904	-1.143	1.0	N	0.749	0.474	0.69617267371	gnomAD-2.1.1	3.63E-05	None	None	None	None	N	None	0	2.60854E-04	None	0	0	None	0	None	0	0	0
R/C	rs753874904	-1.143	1.0	N	0.749	0.474	0.69617267371	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	1.47E-05	0	0
R/C	rs753874904	-1.143	1.0	N	0.749	0.474	0.69617267371	gnomAD-4.0.0	2.16904E-05	None	None	None	None	N	None	0	2.33396E-04	None	0	0	None	0	0	1.69524E-05	1.09789E-05	0
R/G	rs753874904	-1.653	1.0	N	0.679	0.441	0.588775385127	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
R/G	rs753874904	-1.653	1.0	N	0.679	0.441	0.588775385127	gnomAD-4.0.0	1.36843E-06	None	None	None	None	N	None	0	0	None	0	5.03829E-05	None	0	0	0	0	0
R/H	rs575939045	-1.619	1.0	N	0.751	0.37	None	gnomAD-2.1.1	7.51E-05	None	None	None	None	N	None	0	1.13173E-04	None	0	0	None	3.27E-05	None	0	1.09878E-04	2.81057E-04
R/H	rs575939045	-1.619	1.0	N	0.751	0.37	None	gnomAD-3.1.2	1.1177E-04	None	None	None	None	N	None	4.83E-05	6.55E-05	0	0	0	None	0	0	2.05852E-04	0	0
R/H	rs575939045	-1.619	1.0	N	0.751	0.37	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	1E-03	None	None	None	0	None
R/H	rs575939045	-1.619	1.0	N	0.751	0.37	None	gnomAD-4.0.0	1.50579E-04	None	None	None	None	N	None	2.6666E-05	4.99983E-05	None	0	0	None	1.5624E-05	0	1.95802E-04	1.09794E-05	8.0023E-05
R/L	rs575939045	None	1.0	N	0.679	0.423	0.575080649919	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
R/L	rs575939045	None	1.0	N	0.679	0.423	0.575080649919	gnomAD-4.0.0	6.57471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07039E-04	0
R/S	None	None	1.0	N	0.707	0.418	0.385906861911	gnomAD-4.0.0	6.84216E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65656E-05

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	0.785	likely_pathogenic	0.7413	pathogenic	-0.577	Destabilizing	0.999	D	0.513	neutral	None	None	None	None	N
R/C	0.6432	likely_pathogenic	0.4976	ambiguous	-0.526	Destabilizing	1.0	D	0.749	deleterious	N	0.500101194	None	None	N
R/D	0.8069	likely_pathogenic	0.7956	pathogenic	0.055	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
R/E	0.6538	likely_pathogenic	0.6093	pathogenic	0.17	Stabilizing	0.999	D	0.579	neutral	None	None	None	None	N
R/F	0.8808	likely_pathogenic	0.8514	pathogenic	-0.494	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
R/G	0.6262	likely_pathogenic	0.5804	pathogenic	-0.875	Destabilizing	1.0	D	0.679	prob.neutral	N	0.471828722	None	None	N
R/H	0.2573	likely_benign	0.2158	benign	-1.23	Destabilizing	1.0	D	0.751	deleterious	N	0.462789821	None	None	N
R/I	0.6693	likely_pathogenic	0.5922	pathogenic	0.213	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
R/K	0.2607	likely_benign	0.2419	benign	-0.569	Destabilizing	0.998	D	0.477	neutral	None	None	None	None	N
R/L	0.6151	likely_pathogenic	0.5584	ambiguous	0.213	Stabilizing	1.0	D	0.679	prob.neutral	N	0.476121136	None	None	N
R/M	0.6919	likely_pathogenic	0.6204	pathogenic	-0.138	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
R/N	0.7656	likely_pathogenic	0.7347	pathogenic	-0.077	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
R/P	0.9131	likely_pathogenic	0.9089	pathogenic	-0.029	Destabilizing	1.0	D	0.678	prob.neutral	N	0.499594215	None	None	N
R/Q	0.2797	likely_benign	0.2347	benign	-0.234	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
R/S	0.8525	likely_pathogenic	0.8146	pathogenic	-0.784	Destabilizing	1.0	D	0.707	prob.neutral	N	0.514742276	None	None	N
R/T	0.6171	likely_pathogenic	0.5433	ambiguous	-0.491	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
R/V	0.7613	likely_pathogenic	0.7051	pathogenic	-0.029	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
R/W	0.4988	ambiguous	0.4123	ambiguous	-0.226	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
R/Y	0.6929	likely_pathogenic	0.6171	pathogenic	0.098	Stabilizing	1.0	D	0.707	prob.neutral	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.