TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33332	100219;100220;100221	chr2:178537115;178537114;178537113	chr2:179401842;179401841;179401840
N2AB	31691	95296;95297;95298	chr2:178537115;178537114;178537113	chr2:179401842;179401841;179401840
N2A	30764	92515;92516;92517	chr2:178537115;178537114;178537113	chr2:179401842;179401841;179401840
N2B	24267	73024;73025;73026	chr2:178537115;178537114;178537113	chr2:179401842;179401841;179401840
Novex-1	24392	73399;73400;73401	chr2:178537115;178537114;178537113	chr2:179401842;179401841;179401840
Novex-2	24459	73600;73601;73602	chr2:178537115;178537114;178537113	chr2:179401842;179401841;179401840
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-130
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.3024
• 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
E/G	rs1407789736	-1.485	1.0	N	0.691	0.574	0.503311249505	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
E/G	rs1407789736	-1.485	1.0	N	0.691	0.574	0.503311249505	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1407789736	-1.485	1.0	N	0.691	0.574	0.503311249505	gnomAD-4.0.0	4.3393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93423E-06	0	0
E/K	rs1327630158	-0.817	0.999	N	0.573	0.438	0.424908009808	gnomAD-4.0.0	1.59249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85966E-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
E/A	0.2844	likely_benign	0.2845	benign	-0.818	Destabilizing	0.999	D	0.656	neutral	N	0.473561285	None	None	N
E/C	0.9494	likely_pathogenic	0.9564	pathogenic	-0.419	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/D	0.3324	likely_benign	0.2937	benign	-1.074	Destabilizing	0.999	D	0.454	neutral	N	0.42859309	None	None	N
E/F	0.9274	likely_pathogenic	0.9301	pathogenic	-0.168	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/G	0.503	ambiguous	0.5027	ambiguous	-1.178	Destabilizing	1.0	D	0.691	prob.neutral	N	0.479512767	None	None	N
E/H	0.7938	likely_pathogenic	0.8019	pathogenic	-0.297	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
E/I	0.5878	likely_pathogenic	0.5957	pathogenic	0.16	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/K	0.3074	likely_benign	0.3323	benign	-0.39	Destabilizing	0.999	D	0.573	neutral	N	0.515094567	None	None	N
E/L	0.6014	likely_pathogenic	0.5925	pathogenic	0.16	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/M	0.7041	likely_pathogenic	0.6983	pathogenic	0.522	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/N	0.5587	ambiguous	0.5644	pathogenic	-0.967	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/P	0.5853	likely_pathogenic	0.5659	pathogenic	-0.145	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Q	0.2865	likely_benign	0.2995	benign	-0.846	Destabilizing	1.0	D	0.603	neutral	N	0.50728316	None	None	N
E/R	0.5313	ambiguous	0.5666	pathogenic	-0.046	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/S	0.4607	ambiguous	0.4692	ambiguous	-1.238	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
E/T	0.4994	ambiguous	0.4965	ambiguous	-0.935	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/V	0.3985	ambiguous	0.3972	ambiguous	-0.145	Destabilizing	1.0	D	0.781	deleterious	N	0.500250368	None	None	N
E/W	0.9808	likely_pathogenic	0.9812	pathogenic	0.147	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/Y	0.9025	likely_pathogenic	0.9045	pathogenic	0.117	Stabilizing	1.0	D	0.763	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.