TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9757	29494;29495;29496	chr2:178706605;178706604;178706603	chr2:179571332;179571331;179571330
N2AB	9440	28543;28544;28545	chr2:178706605;178706604;178706603	chr2:179571332;179571331;179571330
N2A	8513	25762;25763;25764	chr2:178706605;178706604;178706603	chr2:179571332;179571331;179571330
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-83
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.3488
• 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/Q	None	None	0.957	None	0.313	0.234	0.374970422459	gnomAD-4.0.0	1.59097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85771E-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	0.5537	ambiguous	0.4298	ambiguous	-1.031	Destabilizing	0.996	D	0.575	neutral	None	None	None	None	N
E/C	0.9773	likely_pathogenic	0.9629	pathogenic	-0.582	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.7514	likely_pathogenic	0.5998	pathogenic	-1.449	Destabilizing	0.998	D	0.47	neutral	None	None	None	None	N
E/F	0.9586	likely_pathogenic	0.9222	pathogenic	-0.464	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/G	0.8429	likely_pathogenic	0.7137	pathogenic	-1.465	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
E/H	0.883	likely_pathogenic	0.7981	pathogenic	-0.724	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/I	0.5422	ambiguous	0.4834	ambiguous	0.185	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/K	0.7013	likely_pathogenic	0.5606	ambiguous	-0.919	Destabilizing	0.992	D	0.504	neutral	None	None	None	None	N
E/L	0.8093	likely_pathogenic	0.7095	pathogenic	0.185	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/M	0.751	likely_pathogenic	0.6674	pathogenic	0.781	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/N	0.862	likely_pathogenic	0.7548	pathogenic	-1.378	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9987	pathogenic	-0.201	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/Q	0.342	ambiguous	0.2594	benign	-1.162	Destabilizing	0.957	D	0.313	neutral	None	None	None	None	N
E/R	0.8027	likely_pathogenic	0.6935	pathogenic	-0.73	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/S	0.6829	likely_pathogenic	0.5624	ambiguous	-1.894	Destabilizing	0.997	D	0.559	neutral	None	None	None	None	N
E/T	0.5526	ambiguous	0.4745	ambiguous	-1.506	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/V	0.3613	ambiguous	0.3032	benign	-0.201	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
E/W	0.9894	likely_pathogenic	0.978	pathogenic	-0.307	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.9536	likely_pathogenic	0.9072	pathogenic	-0.194	Destabilizing	1.0	D	0.786	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.