TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28037	84334;84335;84336	chr2:178562023;178562022;178562021	chr2:179426750;179426749;179426748
N2AB	26396	79411;79412;79413	chr2:178562023;178562022;178562021	chr2:179426750;179426749;179426748
N2A	25469	76630;76631;76632	chr2:178562023;178562022;178562021	chr2:179426750;179426749;179426748
N2B	18972	57139;57140;57141	chr2:178562023;178562022;178562021	chr2:179426750;179426749;179426748
Novex-1	19097	57514;57515;57516	chr2:178562023;178562022;178562021	chr2:179426750;179426749;179426748
Novex-2	19164	57715;57716;57717	chr2:178562023;178562022;178562021	chr2:179426750;179426749;179426748
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-142
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.1412
• 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	rs754285119	-0.671	0.002	N	0.291	0.272	0.250579442822	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
V/L	rs754285119	-0.671	0.002	N	0.291	0.272	0.250579442822	gnomAD-4.0.0	2.3269E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.96853E-05	0	1.65728E-05

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	0.3738	ambiguous	0.4248	ambiguous	-2.169	Highly Destabilizing	0.012	N	0.345	neutral	N	0.383535591	None	None	N
V/C	0.8599	likely_pathogenic	0.8606	pathogenic	-2.327	Highly Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
V/D	0.987	likely_pathogenic	0.9913	pathogenic	-2.666	Highly Destabilizing	0.966	D	0.815	deleterious	N	0.514835218	None	None	N
V/E	0.9706	likely_pathogenic	0.9801	pathogenic	-2.472	Highly Destabilizing	0.949	D	0.786	deleterious	None	None	None	None	N
V/F	0.4731	ambiguous	0.5084	ambiguous	-1.405	Destabilizing	0.934	D	0.786	deleterious	N	0.514581729	None	None	N
V/G	0.6828	likely_pathogenic	0.738	pathogenic	-2.677	Highly Destabilizing	0.669	D	0.767	deleterious	N	0.515730151	None	None	N
V/H	0.9872	likely_pathogenic	0.9905	pathogenic	-2.275	Highly Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
V/I	0.0778	likely_benign	0.0757	benign	-0.761	Destabilizing	0.454	N	0.586	neutral	N	0.495410807	None	None	N
V/K	0.979	likely_pathogenic	0.9843	pathogenic	-1.751	Destabilizing	0.949	D	0.785	deleterious	None	None	None	None	N
V/L	0.177	likely_benign	0.1823	benign	-0.761	Destabilizing	0.002	N	0.291	neutral	N	0.429745962	None	None	N
V/M	0.3209	likely_benign	0.3449	ambiguous	-1.14	Destabilizing	0.949	D	0.701	prob.neutral	None	None	None	None	N
V/N	0.9554	likely_pathogenic	0.9656	pathogenic	-2.069	Highly Destabilizing	0.974	D	0.821	deleterious	None	None	None	None	N
V/P	0.9687	likely_pathogenic	0.9749	pathogenic	-1.204	Destabilizing	0.974	D	0.803	deleterious	None	None	None	None	N
V/Q	0.9576	likely_pathogenic	0.9691	pathogenic	-1.974	Destabilizing	0.974	D	0.799	deleterious	None	None	None	None	N
V/R	0.9577	likely_pathogenic	0.9685	pathogenic	-1.546	Destabilizing	0.974	D	0.82	deleterious	None	None	None	None	N
V/S	0.7899	likely_pathogenic	0.8355	pathogenic	-2.753	Highly Destabilizing	0.728	D	0.753	deleterious	None	None	None	None	N
V/T	0.6573	likely_pathogenic	0.713	pathogenic	-2.409	Highly Destabilizing	0.842	D	0.657	neutral	None	None	None	None	N
V/W	0.9888	likely_pathogenic	0.9907	pathogenic	-1.767	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
V/Y	0.9486	likely_pathogenic	0.9546	pathogenic	-1.435	Destabilizing	0.974	D	0.787	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.