TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32885	98878;98879;98880	chr2:178539412;178539411;178539410	chr2:179404139;179404138;179404137
N2AB	31244	93955;93956;93957	chr2:178539412;178539411;178539410	chr2:179404139;179404138;179404137
N2A	30317	91174;91175;91176	chr2:178539412;178539411;178539410	chr2:179404139;179404138;179404137
N2B	23820	71683;71684;71685	chr2:178539412;178539411;178539410	chr2:179404139;179404138;179404137
Novex-1	23945	72058;72059;72060	chr2:178539412;178539411;178539410	chr2:179404139;179404138;179404137
Novex-2	24012	72259;72260;72261	chr2:178539412;178539411;178539410	chr2:179404139;179404138;179404137
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: Fn3-127
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.7459
• 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/K	None	None	0.919	N	0.525	0.132	0.252162846088	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.1334	likely_benign	0.1514	benign	0.018	Stabilizing	0.958	D	0.539	neutral	N	0.470404348	None	None	N
E/C	0.7881	likely_pathogenic	0.8158	pathogenic	-0.092	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
E/D	0.106	likely_benign	0.1095	benign	-0.215	Destabilizing	0.005	N	0.173	neutral	N	0.421613111	None	None	N
E/F	0.6876	likely_pathogenic	0.7133	pathogenic	-0.067	Destabilizing	0.997	D	0.748	deleterious	None	None	None	None	N
E/G	0.1308	likely_benign	0.1444	benign	-0.093	Destabilizing	0.919	D	0.55	neutral	N	0.458130742	None	None	N
E/H	0.412	ambiguous	0.4373	ambiguous	0.506	Stabilizing	0.997	D	0.537	neutral	None	None	None	None	N
E/I	0.3116	likely_benign	0.3374	benign	0.253	Stabilizing	0.997	D	0.756	deleterious	None	None	None	None	N
E/K	0.1035	likely_benign	0.1123	benign	0.457	Stabilizing	0.919	D	0.525	neutral	N	0.462382298	None	None	N
E/L	0.3235	likely_benign	0.3603	ambiguous	0.253	Stabilizing	0.991	D	0.726	deleterious	None	None	None	None	N
E/M	0.3937	ambiguous	0.4263	ambiguous	0.053	Stabilizing	0.999	D	0.736	deleterious	None	None	None	None	N
E/N	0.2116	likely_benign	0.2323	benign	0.307	Stabilizing	0.938	D	0.568	neutral	None	None	None	None	N
E/P	0.3282	likely_benign	0.3966	ambiguous	0.193	Stabilizing	0.997	D	0.585	neutral	None	None	None	None	N
E/Q	0.133	likely_benign	0.1434	benign	0.302	Stabilizing	0.958	D	0.565	neutral	N	0.500900614	None	None	N
E/R	0.1822	likely_benign	0.1915	benign	0.664	Stabilizing	0.991	D	0.593	neutral	None	None	None	None	N
E/S	0.1556	likely_benign	0.1724	benign	0.136	Stabilizing	0.938	D	0.521	neutral	None	None	None	None	N
E/T	0.1728	likely_benign	0.1896	benign	0.231	Stabilizing	0.968	D	0.577	neutral	None	None	None	None	N
E/V	0.1899	likely_benign	0.2081	benign	0.193	Stabilizing	0.996	D	0.623	neutral	N	0.510634818	None	None	N
E/W	0.8124	likely_pathogenic	0.8338	pathogenic	-0.037	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
E/Y	0.5717	likely_pathogenic	0.5889	pathogenic	0.158	Stabilizing	0.997	D	0.739	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.