TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22621	68086;68087;68088	chr2:178579169;178579168;178579167	chr2:179443896;179443895;179443894
N2AB	20980	63163;63164;63165	chr2:178579169;178579168;178579167	chr2:179443896;179443895;179443894
N2A	20053	60382;60383;60384	chr2:178579169;178579168;178579167	chr2:179443896;179443895;179443894
N2B	13556	40891;40892;40893	chr2:178579169;178579168;178579167	chr2:179443896;179443895;179443894
Novex-1	13681	41266;41267;41268	chr2:178579169;178579168;178579167	chr2:179443896;179443895;179443894
Novex-2	13748	41467;41468;41469	chr2:178579169;178579168;178579167	chr2:179443896;179443895;179443894
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: Ig-127
• Domain position: 62
• Structural Position: 154
• Q(SASA): 0.1961
• 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	None	None	1.0	D	0.772	0.793	0.810653237695	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88267E-05	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	0.9973	likely_pathogenic	0.9971	pathogenic	-1.826	Destabilizing	0.992	D	0.782	deleterious	None	None	None	None	N
Y/C	0.9633	likely_pathogenic	0.9602	pathogenic	-1.204	Destabilizing	1.0	D	0.772	deleterious	D	0.620456015	None	None	N
Y/D	0.9979	likely_pathogenic	0.9978	pathogenic	-1.989	Destabilizing	0.999	D	0.822	deleterious	D	0.620456015	None	None	N
Y/E	0.9992	likely_pathogenic	0.9991	pathogenic	-1.741	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
Y/F	0.3069	likely_benign	0.2878	benign	-0.397	Destabilizing	0.121	N	0.378	neutral	D	0.580830372	None	None	N
Y/G	0.9939	likely_pathogenic	0.9933	pathogenic	-2.274	Highly Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
Y/H	0.9791	likely_pathogenic	0.9772	pathogenic	-1.494	Destabilizing	0.999	D	0.729	prob.delet.	D	0.620254211	None	None	N
Y/I	0.9576	likely_pathogenic	0.9569	pathogenic	-0.369	Destabilizing	0.995	D	0.769	deleterious	None	None	None	None	N
Y/K	0.999	likely_pathogenic	0.9989	pathogenic	-1.235	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
Y/L	0.9369	likely_pathogenic	0.9364	pathogenic	-0.369	Destabilizing	0.967	D	0.719	prob.delet.	None	None	None	None	N
Y/M	0.978	likely_pathogenic	0.9761	pathogenic	-0.516	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
Y/N	0.9865	likely_pathogenic	0.9846	pathogenic	-2.048	Highly Destabilizing	0.999	D	0.804	deleterious	D	0.620456015	None	None	N
Y/P	0.9995	likely_pathogenic	0.9995	pathogenic	-0.866	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
Y/Q	0.9988	likely_pathogenic	0.9986	pathogenic	-1.617	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
Y/R	0.997	likely_pathogenic	0.9967	pathogenic	-1.538	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
Y/S	0.9947	likely_pathogenic	0.9943	pathogenic	-2.482	Highly Destabilizing	0.999	D	0.798	deleterious	D	0.620456015	None	None	N
Y/T	0.9971	likely_pathogenic	0.9968	pathogenic	-2.09	Highly Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
Y/V	0.9471	likely_pathogenic	0.9464	pathogenic	-0.866	Destabilizing	0.983	D	0.77	deleterious	None	None	None	None	N
Y/W	0.861	likely_pathogenic	0.8678	pathogenic	0.253	Stabilizing	1.0	D	0.725	prob.delet.	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.