TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20191	60796;60797;60798	chr2:178591154;178591153;178591152	chr2:179455881;179455880;179455879
N2AB	18550	55873;55874;55875	chr2:178591154;178591153;178591152	chr2:179455881;179455880;179455879
N2A	17623	53092;53093;53094	chr2:178591154;178591153;178591152	chr2:179455881;179455880;179455879
N2B	11126	33601;33602;33603	chr2:178591154;178591153;178591152	chr2:179455881;179455880;179455879
Novex-1	11251	33976;33977;33978	chr2:178591154;178591153;178591152	chr2:179455881;179455880;179455879
Novex-2	11318	34177;34178;34179	chr2:178591154;178591153;178591152	chr2:179455881;179455880;179455879
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: Fn3-34
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.06
• 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/L	rs745806239	-1.039	0.993	N	0.359	0.366	0.416833835346	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	2.23839E-04	None	3.27E-05	None	0	0	0
I/L	rs745806239	-1.039	0.993	N	0.359	0.366	0.416833835346	gnomAD-4.0.0	6.84385E-06	None	None	None	None	N	None	0	0	None	0	1.00959E-04	None	0	0	0	4.63865E-05	3.314E-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	0.9157	likely_pathogenic	0.9318	pathogenic	-2.675	Highly Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
I/C	0.9464	likely_pathogenic	0.9526	pathogenic	-1.626	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
I/D	0.9994	likely_pathogenic	0.9996	pathogenic	-3.349	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
I/E	0.9985	likely_pathogenic	0.9989	pathogenic	-3.013	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
I/F	0.5409	ambiguous	0.569	pathogenic	-1.639	Destabilizing	1.0	D	0.775	deleterious	N	0.467000692	None	None	N
I/G	0.9937	likely_pathogenic	0.9956	pathogenic	-3.292	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
I/H	0.9974	likely_pathogenic	0.9981	pathogenic	-3.077	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
I/K	0.997	likely_pathogenic	0.9977	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
I/L	0.1656	likely_benign	0.1653	benign	-0.81	Destabilizing	0.993	D	0.359	neutral	N	0.3660264	None	None	N
I/M	0.3015	likely_benign	0.3258	benign	-0.896	Destabilizing	1.0	D	0.727	prob.delet.	N	0.471293106	None	None	N
I/N	0.9941	likely_pathogenic	0.9964	pathogenic	-2.784	Highly Destabilizing	1.0	D	0.935	deleterious	N	0.506287075	None	None	N
I/P	0.9973	likely_pathogenic	0.9981	pathogenic	-1.425	Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	N
I/Q	0.9969	likely_pathogenic	0.9977	pathogenic	-2.378	Highly Destabilizing	1.0	D	0.94	deleterious	None	None	None	None	N
I/R	0.9943	likely_pathogenic	0.9957	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
I/S	0.9863	likely_pathogenic	0.9913	pathogenic	-3.286	Highly Destabilizing	1.0	D	0.895	deleterious	N	0.506287075	None	None	N
I/T	0.9716	likely_pathogenic	0.9817	pathogenic	-2.781	Highly Destabilizing	1.0	D	0.829	deleterious	N	0.506033585	None	None	N
I/V	0.1016	likely_benign	0.1025	benign	-1.425	Destabilizing	0.993	D	0.32	neutral	N	0.44314875	None	None	N
I/W	0.9948	likely_pathogenic	0.9958	pathogenic	-2.04	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
I/Y	0.9717	likely_pathogenic	0.9758	pathogenic	-1.824	Destabilizing	1.0	D	0.831	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.