TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7720	23383;23384;23385	chr2:178720604;178720603;178720602	chr2:179585331;179585330;179585329
N2AB	7403	22432;22433;22434	chr2:178720604;178720603;178720602	chr2:179585331;179585330;179585329
N2A	6476	19651;19652;19653	chr2:178720604;178720603;178720602	chr2:179585331;179585330;179585329
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-62
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.317
• 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	rs757989250	-0.882	None	N	0.316	0.058	0.152612264143	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.55E-05	None	0	0	0
I/V	rs757989250	-0.882	None	N	0.316	0.058	0.152612264143	gnomAD-4.0.0	4.77815E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86763E-05	3.02792E-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
I/A	0.2212	likely_benign	0.2516	benign	-1.457	Destabilizing	0.007	N	0.405	neutral	None	None	None	None	N
I/C	0.5589	ambiguous	0.6059	pathogenic	-0.816	Destabilizing	0.001	N	0.395	neutral	None	None	None	None	N
I/D	0.4866	ambiguous	0.5066	ambiguous	-0.968	Destabilizing	0.038	N	0.485	neutral	None	None	None	None	N
I/E	0.3993	ambiguous	0.4225	ambiguous	-0.973	Destabilizing	0.072	N	0.474	neutral	None	None	None	None	N
I/F	0.111	likely_benign	0.1203	benign	-1.002	Destabilizing	0.029	N	0.414	neutral	N	0.495342865	None	None	N
I/G	0.4706	ambiguous	0.5305	ambiguous	-1.763	Destabilizing	0.038	N	0.465	neutral	None	None	None	None	N
I/H	0.2759	likely_benign	0.297	benign	-0.933	Destabilizing	0.214	N	0.485	neutral	None	None	None	None	N
I/K	0.2582	likely_benign	0.2704	benign	-1.051	Destabilizing	0.072	N	0.483	neutral	None	None	None	None	N
I/L	0.0913	likely_benign	0.0984	benign	-0.699	Destabilizing	None	N	0.319	neutral	N	0.395813376	None	None	N
I/M	0.0867	likely_benign	0.0932	benign	-0.547	Destabilizing	0.005	N	0.421	neutral	N	0.416767438	None	None	N
I/N	0.1508	likely_benign	0.1531	benign	-0.845	Destabilizing	None	N	0.473	neutral	N	0.428368512	None	None	N
I/P	0.7782	likely_pathogenic	0.8195	pathogenic	-0.92	Destabilizing	0.356	N	0.541	neutral	None	None	None	None	N
I/Q	0.2744	likely_benign	0.2954	benign	-1.013	Destabilizing	0.356	N	0.536	neutral	None	None	None	None	N
I/R	0.1993	likely_benign	0.2099	benign	-0.44	Destabilizing	0.214	N	0.55	neutral	None	None	None	None	N
I/S	0.1594	likely_benign	0.1715	benign	-1.401	Destabilizing	0.002	N	0.429	neutral	N	0.361047441	None	None	N
I/T	0.1222	likely_benign	0.1314	benign	-1.288	Destabilizing	0.012	N	0.449	neutral	N	0.370221498	None	None	N
I/V	0.0655	likely_benign	0.0686	benign	-0.92	Destabilizing	None	N	0.316	neutral	N	0.385249666	None	None	N
I/W	0.6631	likely_pathogenic	0.7084	pathogenic	-1.074	Destabilizing	0.676	D	0.495	neutral	None	None	None	None	N
I/Y	0.349	ambiguous	0.3596	ambiguous	-0.861	Destabilizing	0.001	N	0.396	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.