TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33758	101497;101498;101499	chr2:178535343;178535342;178535341	chr2:179400070;179400069;179400068
N2AB	32117	96574;96575;96576	chr2:178535343;178535342;178535341	chr2:179400070;179400069;179400068
N2A	31190	93793;93794;93795	chr2:178535343;178535342;178535341	chr2:179400070;179400069;179400068
N2B	24693	74302;74303;74304	chr2:178535343;178535342;178535341	chr2:179400070;179400069;179400068
Novex-1	24818	74677;74678;74679	chr2:178535343;178535342;178535341	chr2:179400070;179400069;179400068
Novex-2	24885	74878;74879;74880	chr2:178535343;178535342;178535341	chr2:179400070;179400069;179400068
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-132
• Domain position: 70
• Structural Position: 104
• Q(SASA): 0.1294
• 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	None	None	1.0	D	0.848	0.894	0.730513430788	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
Y/A	0.9978	likely_pathogenic	0.9976	pathogenic	-2.976	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/C	0.9434	likely_pathogenic	0.9478	pathogenic	-1.946	Destabilizing	1.0	D	0.874	deleterious	D	0.638575526	None	None	N
Y/D	0.9978	likely_pathogenic	0.9974	pathogenic	-2.882	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.664113638	None	None	N
Y/E	0.9992	likely_pathogenic	0.9992	pathogenic	-2.703	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/F	0.4315	ambiguous	0.4404	ambiguous	-1.071	Destabilizing	0.999	D	0.763	deleterious	D	0.583361418	None	None	N
Y/G	0.9935	likely_pathogenic	0.9932	pathogenic	-3.382	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/H	0.978	likely_pathogenic	0.9852	pathogenic	-1.851	Destabilizing	1.0	D	0.848	deleterious	D	0.664113638	None	None	N
Y/I	0.9875	likely_pathogenic	0.9862	pathogenic	-1.653	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.9993	pathogenic	-1.89	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/L	0.9597	likely_pathogenic	0.9507	pathogenic	-1.653	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
Y/M	0.9931	likely_pathogenic	0.9922	pathogenic	-1.561	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/N	0.984	likely_pathogenic	0.9845	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.663911834	None	None	N
Y/P	0.9991	likely_pathogenic	0.9989	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/Q	0.9986	likely_pathogenic	0.9988	pathogenic	-2.361	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/R	0.9962	likely_pathogenic	0.9966	pathogenic	-1.54	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/S	0.9856	likely_pathogenic	0.9845	pathogenic	-3.012	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.664113638	None	None	N
Y/T	0.9965	likely_pathogenic	0.9963	pathogenic	-2.713	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/V	0.9716	likely_pathogenic	0.9691	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/W	0.8448	likely_pathogenic	0.8818	pathogenic	-0.383	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.