TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15248	45967;45968;45969	chr2:178620868;178620867;178620866	chr2:179485595;179485594;179485593
N2AB	13607	41044;41045;41046	chr2:178620868;178620867;178620866	chr2:179485595;179485594;179485593
N2A	12680	38263;38264;38265	chr2:178620868;178620867;178620866	chr2:179485595;179485594;179485593
N2B	6183	18772;18773;18774	chr2:178620868;178620867;178620866	chr2:179485595;179485594;179485593
Novex-1	6308	19147;19148;19149	chr2:178620868;178620867;178620866	chr2:179485595;179485594;179485593
Novex-2	6375	19348;19349;19350	chr2:178620868;178620867;178620866	chr2:179485595;179485594;179485593
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-104
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.6021
• 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
F/I	None	None	0.971	N	0.539	0.441	0.454426139905	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
F/L	None	None	0.822	N	0.547	0.343	0.409937222855	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
F/A	0.5699	likely_pathogenic	0.5717	pathogenic	-0.814	Destabilizing	0.754	D	0.545	neutral	None	None	None	None	N
F/C	0.5692	likely_pathogenic	0.6342	pathogenic	-0.43	Destabilizing	0.997	D	0.601	neutral	N	0.508851495	None	None	N
F/D	0.8388	likely_pathogenic	0.8109	pathogenic	0.63	Stabilizing	0.956	D	0.644	neutral	None	None	None	None	N
F/E	0.8302	likely_pathogenic	0.8275	pathogenic	0.61	Stabilizing	0.915	D	0.565	neutral	None	None	None	None	N
F/G	0.8004	likely_pathogenic	0.7866	pathogenic	-0.975	Destabilizing	0.956	D	0.568	neutral	None	None	None	None	N
F/H	0.6654	likely_pathogenic	0.6759	pathogenic	0.278	Stabilizing	0.994	D	0.563	neutral	None	None	None	None	N
F/I	0.3012	likely_benign	0.3605	ambiguous	-0.412	Destabilizing	0.971	D	0.539	neutral	N	0.494039232	None	None	N
F/K	0.8357	likely_pathogenic	0.8142	pathogenic	-0.164	Destabilizing	0.915	D	0.59	neutral	None	None	None	None	N
F/L	0.8724	likely_pathogenic	0.8934	pathogenic	-0.412	Destabilizing	0.822	D	0.547	neutral	N	0.506602692	None	None	N
F/M	0.6299	likely_pathogenic	0.6658	pathogenic	-0.487	Destabilizing	0.978	D	0.558	neutral	None	None	None	None	N
F/N	0.7004	likely_pathogenic	0.6866	pathogenic	-0.224	Destabilizing	0.956	D	0.652	neutral	None	None	None	None	N
F/P	0.9222	likely_pathogenic	0.9166	pathogenic	-0.529	Destabilizing	0.978	D	0.656	neutral	None	None	None	None	N
F/Q	0.7824	likely_pathogenic	0.7839	pathogenic	-0.219	Destabilizing	0.16	N	0.453	neutral	None	None	None	None	N
F/R	0.6996	likely_pathogenic	0.6722	pathogenic	0.187	Stabilizing	0.915	D	0.654	neutral	None	None	None	None	N
F/S	0.4317	ambiguous	0.4416	ambiguous	-0.807	Destabilizing	0.89	D	0.501	neutral	N	0.488669419	None	None	N
F/T	0.5012	ambiguous	0.5037	ambiguous	-0.738	Destabilizing	0.956	D	0.543	neutral	None	None	None	None	N
F/V	0.2896	likely_benign	0.3472	ambiguous	-0.529	Destabilizing	0.822	D	0.559	neutral	N	0.507322795	None	None	N
F/W	0.6277	likely_pathogenic	0.6151	pathogenic	-0.317	Destabilizing	0.998	D	0.541	neutral	None	None	None	None	N
F/Y	0.2604	likely_benign	0.2752	benign	-0.307	Destabilizing	0.904	D	0.545	neutral	N	0.508658802	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.