TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35733	107422;107423;107424	chr2:178528554;178528553;178528552	chr2:179393281;179393280;179393279
N2AB	34092	102499;102500;102501	chr2:178528554;178528553;178528552	chr2:179393281;179393280;179393279
N2A	33165	99718;99719;99720	chr2:178528554;178528553;178528552	chr2:179393281;179393280;179393279
N2B	26668	80227;80228;80229	chr2:178528554;178528553;178528552	chr2:179393281;179393280;179393279
Novex-1	26793	80602;80603;80604	chr2:178528554;178528553;178528552	chr2:179393281;179393280;179393279
Novex-2	26860	80803;80804;80805	chr2:178528554;178528553;178528552	chr2:179393281;179393280;179393279
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-168
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1867
• Predicted PPI site: I

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/M	rs776237176	-0.958	0.994	N	0.701	0.469	0.373537453441	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	6.54E-05	0	None	0	0	None	0	None	0	0	0
I/V	None	None	0.004	N	0.256	0.138	0.286848849266	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	1.26695E-04	0	None	0	0	None	0	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
I/A	0.4494	ambiguous	0.4293	ambiguous	-2.378	Highly Destabilizing	0.702	D	0.712	prob.delet.	None	None	None	None	I
I/C	0.9099	likely_pathogenic	0.9111	pathogenic	-1.622	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	I
I/D	0.971	likely_pathogenic	0.9655	pathogenic	-2.729	Highly Destabilizing	0.996	D	0.844	deleterious	None	None	None	None	I
I/E	0.9165	likely_pathogenic	0.9062	pathogenic	-2.535	Highly Destabilizing	0.988	D	0.821	deleterious	None	None	None	None	I
I/F	0.4056	ambiguous	0.3856	ambiguous	-1.516	Destabilizing	0.984	D	0.702	prob.neutral	N	0.51394064	None	None	I
I/G	0.9102	likely_pathogenic	0.8985	pathogenic	-2.842	Highly Destabilizing	0.988	D	0.798	deleterious	None	None	None	None	I
I/H	0.9451	likely_pathogenic	0.9393	pathogenic	-2.074	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
I/K	0.8511	likely_pathogenic	0.8325	pathogenic	-1.88	Destabilizing	0.988	D	0.825	deleterious	None	None	None	None	I
I/L	0.2607	likely_benign	0.2528	benign	-1.047	Destabilizing	0.437	N	0.434	neutral	N	0.516132796	None	None	I
I/M	0.1443	likely_benign	0.141	benign	-0.955	Destabilizing	0.994	D	0.701	prob.neutral	N	0.515013029	None	None	I
I/N	0.7772	likely_pathogenic	0.7508	pathogenic	-2.145	Highly Destabilizing	0.995	D	0.844	deleterious	D	0.542018054	None	None	I
I/P	0.92	likely_pathogenic	0.9036	pathogenic	-1.473	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	I
I/Q	0.8947	likely_pathogenic	0.8815	pathogenic	-2.092	Highly Destabilizing	0.996	D	0.838	deleterious	None	None	None	None	I
I/R	0.8017	likely_pathogenic	0.7814	pathogenic	-1.53	Destabilizing	0.988	D	0.845	deleterious	None	None	None	None	I
I/S	0.6602	likely_pathogenic	0.6338	pathogenic	-2.747	Highly Destabilizing	0.984	D	0.801	deleterious	D	0.530408259	None	None	I
I/T	0.2428	likely_benign	0.2316	benign	-2.412	Highly Destabilizing	0.896	D	0.715	prob.delet.	N	0.498060863	None	None	I
I/V	0.1001	likely_benign	0.1005	benign	-1.473	Destabilizing	0.004	N	0.256	neutral	N	0.405431016	None	None	I
I/W	0.9388	likely_pathogenic	0.9337	pathogenic	-1.76	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
I/Y	0.8448	likely_pathogenic	0.8323	pathogenic	-1.488	Destabilizing	0.996	D	0.76	deleterious	None	None	None	None	I

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.