TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20179	60760;60761;60762	chr2:178591190;178591189;178591188	chr2:179455917;179455916;179455915
N2AB	18538	55837;55838;55839	chr2:178591190;178591189;178591188	chr2:179455917;179455916;179455915
N2A	17611	53056;53057;53058	chr2:178591190;178591189;178591188	chr2:179455917;179455916;179455915
N2B	11114	33565;33566;33567	chr2:178591190;178591189;178591188	chr2:179455917;179455916;179455915
Novex-1	11239	33940;33941;33942	chr2:178591190;178591189;178591188	chr2:179455917;179455916;179455915
Novex-2	11306	34141;34142;34143	chr2:178591190;178591189;178591188	chr2:179455917;179455916;179455915
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-34
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.1201
• 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
I/V	rs1370265685	-1.232	0.021	N	0.216	0.071	0.378322506985	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/V	rs1370265685	-1.232	0.021	N	0.216	0.071	0.378322506985	gnomAD-4.0.0	1.77932E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.339E-05	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
I/A	0.8765	likely_pathogenic	0.9252	pathogenic	-2.355	Highly Destabilizing	0.079	N	0.433	neutral	None	None	None	None	N
I/C	0.9218	likely_pathogenic	0.9463	pathogenic	-1.942	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
I/D	0.9961	likely_pathogenic	0.9983	pathogenic	-2.261	Highly Destabilizing	0.997	D	0.8	deleterious	None	None	None	None	N
I/E	0.9888	likely_pathogenic	0.9943	pathogenic	-2.039	Highly Destabilizing	0.991	D	0.795	deleterious	None	None	None	None	N
I/F	0.5902	likely_pathogenic	0.6931	pathogenic	-1.354	Destabilizing	0.988	D	0.731	prob.delet.	N	0.516094644	None	None	N
I/G	0.9838	likely_pathogenic	0.9931	pathogenic	-2.904	Highly Destabilizing	0.939	D	0.772	deleterious	None	None	None	None	N
I/H	0.9912	likely_pathogenic	0.9963	pathogenic	-2.384	Highly Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
I/K	0.98	likely_pathogenic	0.9897	pathogenic	-1.675	Destabilizing	0.991	D	0.797	deleterious	None	None	None	None	N
I/L	0.1795	likely_benign	0.1911	benign	-0.778	Destabilizing	0.509	D	0.531	neutral	N	0.424848204	None	None	N
I/M	0.2067	likely_benign	0.2211	benign	-0.973	Destabilizing	0.988	D	0.672	neutral	N	0.504936288	None	None	N
I/N	0.9654	likely_pathogenic	0.9844	pathogenic	-1.954	Destabilizing	0.996	D	0.806	deleterious	N	0.504414197	None	None	N
I/P	0.9399	likely_pathogenic	0.9551	pathogenic	-1.282	Destabilizing	0.997	D	0.803	deleterious	None	None	None	None	N
I/Q	0.9801	likely_pathogenic	0.9899	pathogenic	-1.798	Destabilizing	0.997	D	0.805	deleterious	None	None	None	None	N
I/R	0.9739	likely_pathogenic	0.9878	pathogenic	-1.525	Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
I/S	0.9531	likely_pathogenic	0.9769	pathogenic	-2.735	Highly Destabilizing	0.852	D	0.738	prob.delet.	N	0.486221037	None	None	N
I/T	0.9219	likely_pathogenic	0.9518	pathogenic	-2.355	Highly Destabilizing	0.92	D	0.709	prob.delet.	N	0.514979924	None	None	N
I/V	0.0809	likely_benign	0.0862	benign	-1.282	Destabilizing	0.021	N	0.216	neutral	N	0.4238537	None	None	N
I/W	0.9835	likely_pathogenic	0.9921	pathogenic	-1.655	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
I/Y	0.9604	likely_pathogenic	0.9798	pathogenic	-1.368	Destabilizing	0.997	D	0.771	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.