TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19742	59449;59450;59451	chr2:178592895;178592894;178592893	chr2:179457622;179457621;179457620
N2AB	18101	54526;54527;54528	chr2:178592895;178592894;178592893	chr2:179457622;179457621;179457620
N2A	17174	51745;51746;51747	chr2:178592895;178592894;178592893	chr2:179457622;179457621;179457620
N2B	10677	32254;32255;32256	chr2:178592895;178592894;178592893	chr2:179457622;179457621;179457620
Novex-1	10802	32629;32630;32631	chr2:178592895;178592894;178592893	chr2:179457622;179457621;179457620
Novex-2	10869	32830;32831;32832	chr2:178592895;178592894;178592893	chr2:179457622;179457621;179457620
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: Fn3-31
• Domain position: 63
• Structural Position: 91
• Q(SASA): 0.2672
• 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/C	rs1559607092	None	0.997	N	0.584	0.388	0.454238212503	gnomAD-4.0.0	5.47446E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29713E-06	1.15947E-05	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	0.9197	likely_pathogenic	0.9052	pathogenic	-2.159	Highly Destabilizing	0.842	D	0.497	neutral	None	None	None	None	N
Y/C	0.3705	ambiguous	0.3238	benign	-1.062	Destabilizing	0.997	D	0.584	neutral	N	0.488046825	None	None	N
Y/D	0.9468	likely_pathogenic	0.9358	pathogenic	-1.099	Destabilizing	0.966	D	0.58	neutral	N	0.521231913	None	None	N
Y/E	0.9635	likely_pathogenic	0.9609	pathogenic	-0.981	Destabilizing	0.949	D	0.547	neutral	None	None	None	None	N
Y/F	0.0895	likely_benign	0.0918	benign	-0.75	Destabilizing	0.005	N	0.203	neutral	N	0.424264706	None	None	N
Y/G	0.8823	likely_pathogenic	0.8621	pathogenic	-2.501	Highly Destabilizing	0.915	D	0.543	neutral	None	None	None	None	N
Y/H	0.5398	ambiguous	0.557	ambiguous	-0.947	Destabilizing	0.028	N	0.443	neutral	N	0.502592203	None	None	N
Y/I	0.7986	likely_pathogenic	0.7646	pathogenic	-1.105	Destabilizing	0.728	D	0.445	neutral	None	None	None	None	N
Y/K	0.9412	likely_pathogenic	0.9406	pathogenic	-1.388	Destabilizing	0.949	D	0.55	neutral	None	None	None	None	N
Y/L	0.7068	likely_pathogenic	0.6756	pathogenic	-1.105	Destabilizing	0.525	D	0.44	neutral	None	None	None	None	N
Y/M	0.8038	likely_pathogenic	0.7789	pathogenic	-0.853	Destabilizing	0.974	D	0.509	neutral	None	None	None	None	N
Y/N	0.8102	likely_pathogenic	0.7991	pathogenic	-1.882	Destabilizing	0.934	D	0.545	neutral	N	0.520978424	None	None	N
Y/P	0.9975	likely_pathogenic	0.9958	pathogenic	-1.454	Destabilizing	0.991	D	0.603	neutral	None	None	None	None	N
Y/Q	0.9126	likely_pathogenic	0.9134	pathogenic	-1.702	Destabilizing	0.949	D	0.497	neutral	None	None	None	None	N
Y/R	0.8979	likely_pathogenic	0.8999	pathogenic	-1.08	Destabilizing	0.949	D	0.558	neutral	None	None	None	None	N
Y/S	0.8742	likely_pathogenic	0.85	pathogenic	-2.354	Highly Destabilizing	0.801	D	0.524	neutral	N	0.497847739	None	None	N
Y/T	0.9369	likely_pathogenic	0.923	pathogenic	-2.132	Highly Destabilizing	0.974	D	0.55	neutral	None	None	None	None	N
Y/V	0.7558	likely_pathogenic	0.7125	pathogenic	-1.454	Destabilizing	0.842	D	0.415	neutral	None	None	None	None	N
Y/W	0.5585	ambiguous	0.5377	ambiguous	-0.341	Destabilizing	0.991	D	0.463	neutral	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.