TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24395	73408;73409;73410	chr2:178572949;178572948;178572947	chr2:179437676;179437675;179437674
N2AB	22754	68485;68486;68487	chr2:178572949;178572948;178572947	chr2:179437676;179437675;179437674
N2A	21827	65704;65705;65706	chr2:178572949;178572948;178572947	chr2:179437676;179437675;179437674
N2B	15330	46213;46214;46215	chr2:178572949;178572948;178572947	chr2:179437676;179437675;179437674
Novex-1	15455	46588;46589;46590	chr2:178572949;178572948;178572947	chr2:179437676;179437675;179437674
Novex-2	15522	46789;46790;46791	chr2:178572949;178572948;178572947	chr2:179437676;179437675;179437674
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-65
• Domain position: 73
• Structural Position: 104
• Q(SASA): 0.1091
• 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
Y/H	rs1489927926	-2.206	1.0	D	0.847	0.888	0.802717274073	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66389E-04
Y/H	rs1489927926	-2.206	1.0	D	0.847	0.888	0.802717274073	gnomAD-4.0.0	1.59254E-06	None	None	None	None	N	None	0	2.28822E-05	None	0	0	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
Y/A	0.992	likely_pathogenic	0.9896	pathogenic	-3.235	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
Y/C	0.8394	likely_pathogenic	0.8217	pathogenic	-1.936	Destabilizing	1.0	D	0.881	deleterious	D	0.668524766	None	None	N
Y/D	0.9944	likely_pathogenic	0.9932	pathogenic	-3.804	Highly Destabilizing	1.0	D	0.89	deleterious	D	0.684544127	None	None	N
Y/E	0.9969	likely_pathogenic	0.9962	pathogenic	-3.591	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/F	0.291	likely_benign	0.2719	benign	-1.198	Destabilizing	0.999	D	0.771	deleterious	D	0.631651665	None	None	N
Y/G	0.9795	likely_pathogenic	0.9756	pathogenic	-3.653	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/H	0.911	likely_pathogenic	0.9042	pathogenic	-2.313	Highly Destabilizing	1.0	D	0.847	deleterious	D	0.668524766	None	None	N
Y/I	0.9467	likely_pathogenic	0.9337	pathogenic	-1.833	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/K	0.9918	likely_pathogenic	0.9903	pathogenic	-2.49	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/L	0.9243	likely_pathogenic	0.9045	pathogenic	-1.833	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
Y/M	0.9618	likely_pathogenic	0.9516	pathogenic	-1.557	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/N	0.9337	likely_pathogenic	0.9239	pathogenic	-3.342	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.684342323	None	None	N
Y/P	0.9986	likely_pathogenic	0.9984	pathogenic	-2.318	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
Y/Q	0.9919	likely_pathogenic	0.9907	pathogenic	-3.069	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/R	0.9801	likely_pathogenic	0.9785	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/S	0.9827	likely_pathogenic	0.979	pathogenic	-3.635	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.659006016	None	None	N
Y/T	0.9908	likely_pathogenic	0.9885	pathogenic	-3.302	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/V	0.9125	likely_pathogenic	0.8989	pathogenic	-2.318	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/W	0.8376	likely_pathogenic	0.8235	pathogenic	-0.525	Destabilizing	1.0	D	0.825	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.