TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6273	19042;19043;19044	chr2:178729339;178729338;178729337	chr2:179594066;179594065;179594064
N2AB	5956	18091;18092;18093	chr2:178729339;178729338;178729337	chr2:179594066;179594065;179594064
N2A	5029	15310;15311;15312	chr2:178729339;178729338;178729337	chr2:179594066;179594065;179594064
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-46
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0486
• 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	None	None	0.004	N	0.481	0.201	0.180583059064	gnomAD-4.0.0	4.79096E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29809E-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
V/A	0.3585	ambiguous	0.3849	ambiguous	-1.824	Destabilizing	0.001	N	0.295	neutral	N	0.437138002	None	None	N
V/C	0.8537	likely_pathogenic	0.8887	pathogenic	-1.473	Destabilizing	0.935	D	0.803	deleterious	None	None	None	None	N
V/D	0.98	likely_pathogenic	0.9845	pathogenic	-2.333	Highly Destabilizing	0.555	D	0.845	deleterious	None	None	None	None	N
V/E	0.9663	likely_pathogenic	0.972	pathogenic	-2.029	Highly Destabilizing	0.484	N	0.799	deleterious	D	0.53837075	None	None	N
V/F	0.4112	ambiguous	0.5053	ambiguous	-0.974	Destabilizing	0.38	N	0.815	deleterious	None	None	None	None	N
V/G	0.7014	likely_pathogenic	0.7456	pathogenic	-2.44	Highly Destabilizing	0.117	N	0.789	deleterious	N	0.498617068	None	None	N
V/H	0.9778	likely_pathogenic	0.9847	pathogenic	-2.402	Highly Destabilizing	0.935	D	0.838	deleterious	None	None	None	None	N
V/I	0.0679	likely_benign	0.0733	benign	-0.058	Destabilizing	None	N	0.228	neutral	N	0.488946195	None	None	N
V/K	0.9783	likely_pathogenic	0.9826	pathogenic	-1.164	Destabilizing	0.555	D	0.801	deleterious	None	None	None	None	N
V/L	0.2493	likely_benign	0.306	benign	-0.058	Destabilizing	0.004	N	0.481	neutral	N	0.495703779	None	None	N
V/M	0.344	ambiguous	0.4081	ambiguous	-0.444	Destabilizing	0.38	N	0.691	prob.neutral	None	None	None	None	N
V/N	0.9368	likely_pathogenic	0.9527	pathogenic	-1.718	Destabilizing	0.791	D	0.857	deleterious	None	None	None	None	N
V/P	0.956	likely_pathogenic	0.9739	pathogenic	-0.623	Destabilizing	0.555	D	0.833	deleterious	None	None	None	None	N
V/Q	0.9545	likely_pathogenic	0.965	pathogenic	-1.369	Destabilizing	0.791	D	0.833	deleterious	None	None	None	None	N
V/R	0.946	likely_pathogenic	0.957	pathogenic	-1.426	Destabilizing	0.555	D	0.856	deleterious	None	None	None	None	N
V/S	0.7006	likely_pathogenic	0.748	pathogenic	-2.354	Highly Destabilizing	0.081	N	0.773	deleterious	None	None	None	None	N
V/T	0.6014	likely_pathogenic	0.6647	pathogenic	-1.875	Destabilizing	0.149	N	0.676	prob.neutral	None	None	None	None	N
V/W	0.9781	likely_pathogenic	0.9858	pathogenic	-1.483	Destabilizing	0.935	D	0.825	deleterious	None	None	None	None	N
V/Y	0.91	likely_pathogenic	0.9401	pathogenic	-1.085	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.