TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9120	27583;27584;27585	chr2:178712564;178712563;178712562	chr2:179577291;179577290;179577289
N2AB	8803	26632;26633;26634	chr2:178712564;178712563;178712562	chr2:179577291;179577290;179577289
N2A	7876	23851;23852;23853	chr2:178712564;178712563;178712562	chr2:179577291;179577290;179577289
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-77
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4639
• 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
D/Y	None	None	0.999	N	0.651	0.38	0.574978667741	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
D/A	0.2868	likely_benign	0.2759	benign	-0.344	Destabilizing	0.885	D	0.462	neutral	N	0.459570136	None	None	N
D/C	0.8147	likely_pathogenic	0.7607	pathogenic	-0.137	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
D/E	0.3645	ambiguous	0.3236	benign	-0.381	Destabilizing	0.939	D	0.392	neutral	N	0.502098266	None	None	N
D/F	0.8249	likely_pathogenic	0.7845	pathogenic	-0.032	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
D/G	0.2285	likely_benign	0.2272	benign	-0.605	Destabilizing	0.885	D	0.438	neutral	N	0.473786824	None	None	N
D/H	0.4435	ambiguous	0.4017	ambiguous	0.056	Stabilizing	0.998	D	0.597	neutral	N	0.489626581	None	None	N
D/I	0.6281	likely_pathogenic	0.5829	pathogenic	0.312	Stabilizing	0.993	D	0.681	prob.neutral	None	None	None	None	N
D/K	0.665	likely_pathogenic	0.5989	pathogenic	0.108	Stabilizing	0.986	D	0.58	neutral	None	None	None	None	N
D/L	0.6911	likely_pathogenic	0.6354	pathogenic	0.312	Stabilizing	0.993	D	0.665	neutral	None	None	None	None	N
D/M	0.8505	likely_pathogenic	0.8137	pathogenic	0.417	Stabilizing	0.999	D	0.646	neutral	None	None	None	None	N
D/N	0.0932	likely_benign	0.0977	benign	-0.322	Destabilizing	0.1	N	0.26	neutral	N	0.479970768	None	None	N
D/P	0.7183	likely_pathogenic	0.6972	pathogenic	0.117	Stabilizing	0.993	D	0.64	neutral	None	None	None	None	N
D/Q	0.6077	likely_pathogenic	0.5563	ambiguous	-0.23	Destabilizing	0.993	D	0.567	neutral	None	None	None	None	N
D/R	0.6593	likely_pathogenic	0.5872	pathogenic	0.364	Stabilizing	0.986	D	0.642	neutral	None	None	None	None	N
D/S	0.1534	likely_benign	0.1492	benign	-0.453	Destabilizing	0.647	D	0.251	neutral	None	None	None	None	N
D/T	0.3619	ambiguous	0.3297	benign	-0.24	Destabilizing	0.91	D	0.533	neutral	None	None	None	None	N
D/V	0.4673	ambiguous	0.4184	ambiguous	0.117	Stabilizing	0.991	D	0.681	prob.neutral	N	0.492486963	None	None	N
D/W	0.9601	likely_pathogenic	0.9422	pathogenic	0.16	Stabilizing	0.999	D	0.649	neutral	None	None	None	None	N
D/Y	0.3997	ambiguous	0.35	ambiguous	0.22	Stabilizing	0.999	D	0.651	neutral	N	0.516124626	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.