TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3161	9706;9707;9708	chr2:178766603;178766602;178766601	chr2:179631330;179631329;179631328
N2AB	3161	9706;9707;9708	chr2:178766603;178766602;178766601	chr2:179631330;179631329;179631328
N2A	3161	9706;9707;9708	chr2:178766603;178766602;178766601	chr2:179631330;179631329;179631328
N2B	3115	9568;9569;9570	chr2:178766603;178766602;178766601	chr2:179631330;179631329;179631328
Novex-1	3115	9568;9569;9570	chr2:178766603;178766602;178766601	chr2:179631330;179631329;179631328
Novex-2	3115	9568;9569;9570	chr2:178766603;178766602;178766601	chr2:179631330;179631329;179631328
Novex-3	3161	9706;9707;9708	chr2:178766603;178766602;178766601	chr2:179631330;179631329;179631328

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-22
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.8177
• 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
K/E	rs113021611	None	0.939	D	0.587	0.411	0.385906861911	gnomAD-4.0.0	1.36959E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80058E-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
K/A	0.7207	likely_pathogenic	0.8458	pathogenic	0.007	Stabilizing	0.953	D	0.608	neutral	None	None	None	None	N
K/C	0.8966	likely_pathogenic	0.9354	pathogenic	-0.146	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
K/D	0.7582	likely_pathogenic	0.8347	pathogenic	0.015	Stabilizing	0.993	D	0.611	neutral	None	None	None	None	N
K/E	0.3662	ambiguous	0.5449	ambiguous	0.042	Stabilizing	0.939	D	0.587	neutral	D	0.579821783	None	None	N
K/F	0.9412	likely_pathogenic	0.9692	pathogenic	-0.027	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
K/G	0.5471	ambiguous	0.5532	ambiguous	-0.244	Destabilizing	0.993	D	0.61	neutral	None	None	None	None	N
K/H	0.4862	ambiguous	0.5122	ambiguous	-0.521	Destabilizing	0.998	D	0.618	neutral	None	None	None	None	N
K/I	0.845	likely_pathogenic	0.9526	pathogenic	0.604	Stabilizing	0.991	D	0.648	neutral	D	0.585420739	None	None	N
K/L	0.6901	likely_pathogenic	0.8196	pathogenic	0.604	Stabilizing	0.986	D	0.61	neutral	None	None	None	None	N
K/M	0.514	ambiguous	0.6884	pathogenic	0.374	Stabilizing	0.999	D	0.616	neutral	None	None	None	None	N
K/N	0.5088	ambiguous	0.6025	pathogenic	0.172	Stabilizing	0.982	D	0.623	neutral	N	0.505704947	None	None	N
K/P	0.9455	likely_pathogenic	0.9878	pathogenic	0.435	Stabilizing	0.998	D	0.609	neutral	None	None	None	None	N
K/Q	0.2237	likely_benign	0.265	benign	0.006	Stabilizing	0.982	D	0.632	neutral	D	0.58305132	None	None	N
K/R	0.106	likely_benign	0.1185	benign	-0.108	Destabilizing	0.046	N	0.364	neutral	N	0.502236011	None	None	N
K/S	0.6829	likely_pathogenic	0.7869	pathogenic	-0.327	Destabilizing	0.953	D	0.61	neutral	None	None	None	None	N
K/T	0.518	ambiguous	0.7152	pathogenic	-0.14	Destabilizing	0.991	D	0.606	neutral	N	0.5109628	None	None	N
K/V	0.8183	likely_pathogenic	0.9307	pathogenic	0.435	Stabilizing	0.993	D	0.605	neutral	None	None	None	None	N
K/W	0.9064	likely_pathogenic	0.9525	pathogenic	-0.01	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
K/Y	0.8131	likely_pathogenic	0.8822	pathogenic	0.316	Stabilizing	0.998	D	0.627	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.