TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3826	11701;11702;11703	chr2:178741757;178741756;178741755	chr2:179606484;179606483;179606482
N2AB	3509	10750;10751;10752	chr2:178741757;178741756;178741755	chr2:179606484;179606483;179606482
N2A	None	None	chr2:None	chr2:None
N2B	3463	10612;10613;10614	chr2:178741757;178741756;178741755	chr2:179606484;179606483;179606482
Novex-1	3588	10987;10988;10989	chr2:178741757;178741756;178741755	chr2:179606484;179606483;179606482
Novex-2	3655	11188;11189;11190	chr2:178741757;178741756;178741755	chr2:179606484;179606483;179606482
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-27
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1448
• 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
V/L	rs1285885042	-0.642	None	N	0.138	0.041	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.67729E-04	None	0	None	0	0	0
V/L	rs1285885042	-0.642	None	N	0.138	0.041	None	gnomAD-4.0.0	3.18339E-06	None	None	None	None	N	None	0	0	None	0	5.55525E-05	None	0	0	0	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
V/A	0.2159	likely_benign	0.1846	benign	-1.892	Destabilizing	None	N	0.209	neutral	N	0.412490279	None	None	N
V/C	0.8515	likely_pathogenic	0.8072	pathogenic	-1.611	Destabilizing	0.824	D	0.759	deleterious	None	None	None	None	N
V/D	0.7434	likely_pathogenic	0.6879	pathogenic	-1.941	Destabilizing	0.38	N	0.805	deleterious	None	None	None	None	N
V/E	0.6881	likely_pathogenic	0.6417	pathogenic	-1.786	Destabilizing	0.317	N	0.783	deleterious	N	0.434918421	None	None	N
V/F	0.3282	likely_benign	0.2522	benign	-1.169	Destabilizing	0.38	N	0.809	deleterious	None	None	None	None	N
V/G	0.3093	likely_benign	0.2679	benign	-2.385	Highly Destabilizing	0.062	N	0.752	deleterious	N	0.43573682	None	None	N
V/H	0.9148	likely_pathogenic	0.8749	pathogenic	-2.05	Highly Destabilizing	0.935	D	0.77	deleterious	None	None	None	None	N
V/I	0.1056	likely_benign	0.0885	benign	-0.555	Destabilizing	0.001	N	0.185	neutral	None	None	None	None	N
V/K	0.7761	likely_pathogenic	0.7309	pathogenic	-1.449	Destabilizing	0.149	N	0.763	deleterious	None	None	None	None	N
V/L	0.2832	likely_benign	0.1896	benign	-0.555	Destabilizing	None	N	0.138	neutral	N	0.281184867	None	None	N
V/M	0.206	likely_benign	0.1495	benign	-0.669	Destabilizing	0.002	N	0.387	neutral	N	0.345158111	None	None	N
V/N	0.6346	likely_pathogenic	0.5258	ambiguous	-1.549	Destabilizing	0.555	D	0.816	deleterious	None	None	None	None	N
V/P	0.5944	likely_pathogenic	0.5595	ambiguous	-0.97	Destabilizing	0.38	N	0.785	deleterious	None	None	None	None	N
V/Q	0.7616	likely_pathogenic	0.6925	pathogenic	-1.487	Destabilizing	0.555	D	0.797	deleterious	None	None	None	None	N
V/R	0.7502	likely_pathogenic	0.6932	pathogenic	-1.25	Destabilizing	0.38	N	0.805	deleterious	None	None	None	None	N
V/S	0.4483	ambiguous	0.3591	ambiguous	-2.245	Highly Destabilizing	0.081	N	0.695	prob.neutral	None	None	None	None	N
V/T	0.4108	ambiguous	0.3263	benign	-1.945	Destabilizing	0.081	N	0.621	neutral	None	None	None	None	N
V/W	0.948	likely_pathogenic	0.9192	pathogenic	-1.539	Destabilizing	0.935	D	0.771	deleterious	None	None	None	None	N
V/Y	0.8242	likely_pathogenic	0.7583	pathogenic	-1.186	Destabilizing	0.555	D	0.815	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.