TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8700	26323;26324;26325	chr2:178715088;178715087;178715086	chr2:179579815;179579814;179579813
N2AB	8383	25372;25373;25374	chr2:178715088;178715087;178715086	chr2:179579815;179579814;179579813
N2A	7456	22591;22592;22593	chr2:178715088;178715087;178715086	chr2:179579815;179579814;179579813
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: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-72
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.067
• 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/N	rs1404662292	-3.013	1.0	N	0.88	0.545	0.809427183511	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/N	rs1404662292	-3.013	1.0	N	0.88	0.545	0.809427183511	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05
I/V	None	None	0.163	N	0.363	0.103	0.335910606209	gnomAD-4.0.0	1.36847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79905E-06	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	0.741	likely_pathogenic	0.7659	pathogenic	-2.866	Highly Destabilizing	0.968	D	0.726	prob.delet.	None	None	None	None	N
I/C	0.8667	likely_pathogenic	0.8664	pathogenic	-2.191	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
I/D	0.9958	likely_pathogenic	0.9959	pathogenic	-3.493	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/E	0.9899	likely_pathogenic	0.9908	pathogenic	-3.205	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
I/F	0.3428	ambiguous	0.4171	ambiguous	-1.751	Destabilizing	0.987	D	0.72	prob.delet.	N	0.487992818	None	None	N
I/G	0.9625	likely_pathogenic	0.9678	pathogenic	-3.387	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
I/H	0.9727	likely_pathogenic	0.9778	pathogenic	-3.043	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
I/K	0.9768	likely_pathogenic	0.9804	pathogenic	-2.299	Highly Destabilizing	0.998	D	0.858	deleterious	None	None	None	None	N
I/L	0.1023	likely_benign	0.114	benign	-1.27	Destabilizing	0.001	N	0.309	neutral	N	0.297984027	None	None	N
I/M	0.15	likely_benign	0.1793	benign	-1.583	Destabilizing	0.959	D	0.658	neutral	N	0.498036454	None	None	N
I/N	0.9333	likely_pathogenic	0.9405	pathogenic	-2.991	Highly Destabilizing	1.0	D	0.88	deleterious	N	0.478684668	None	None	N
I/P	0.9883	likely_pathogenic	0.9901	pathogenic	-1.799	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
I/Q	0.9708	likely_pathogenic	0.9753	pathogenic	-2.662	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/R	0.9609	likely_pathogenic	0.9678	pathogenic	-2.334	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/S	0.8698	likely_pathogenic	0.8894	pathogenic	-3.424	Highly Destabilizing	1.0	D	0.833	deleterious	N	0.467328362	None	None	N
I/T	0.8138	likely_pathogenic	0.8287	pathogenic	-2.995	Highly Destabilizing	0.999	D	0.757	deleterious	N	0.478684668	None	None	N
I/V	0.0962	likely_benign	0.0891	benign	-1.799	Destabilizing	0.163	N	0.363	neutral	N	0.457824627	None	None	N
I/W	0.963	likely_pathogenic	0.9732	pathogenic	-2.056	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
I/Y	0.8792	likely_pathogenic	0.9057	pathogenic	-1.99	Destabilizing	0.999	D	0.801	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.