TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7870	23833;23834;23835	chr2:178720034;178720033;178720032	chr2:179584761;179584760;179584759
N2AB	7553	22882;22883;22884	chr2:178720034;178720033;178720032	chr2:179584761;179584760;179584759
N2A	6626	20101;20102;20103	chr2:178720034;178720033;178720032	chr2:179584761;179584760;179584759
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-63
• Domain position: 76
• Structural Position: 158
• Q(SASA): 0.0649
• 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	None	None	0.995	N	0.819	0.634	0.86173524933	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.7009	likely_pathogenic	0.5658	pathogenic	-2.839	Highly Destabilizing	0.002	N	0.461	neutral	None	None	None	None	N
I/C	0.9417	likely_pathogenic	0.911	pathogenic	-2.048	Highly Destabilizing	0.905	D	0.775	deleterious	None	None	None	None	N
I/D	0.9986	likely_pathogenic	0.9969	pathogenic	-3.561	Highly Destabilizing	0.997	D	0.811	deleterious	None	None	None	None	N
I/E	0.9949	likely_pathogenic	0.9907	pathogenic	-3.289	Highly Destabilizing	0.968	D	0.779	deleterious	None	None	None	None	N
I/F	0.7865	likely_pathogenic	0.7281	pathogenic	-1.6	Destabilizing	0.783	D	0.709	prob.delet.	N	0.50419234	None	None	N
I/G	0.9711	likely_pathogenic	0.9415	pathogenic	-3.386	Highly Destabilizing	0.4	N	0.739	prob.delet.	None	None	None	None	N
I/H	0.997	likely_pathogenic	0.9943	pathogenic	-2.934	Highly Destabilizing	0.978	D	0.827	deleterious	None	None	None	None	N
I/K	0.9963	likely_pathogenic	0.9927	pathogenic	-2.218	Highly Destabilizing	0.548	D	0.777	deleterious	None	None	None	None	N
I/L	0.3511	ambiguous	0.2691	benign	-1.207	Destabilizing	None	N	0.293	neutral	D	0.528595087	None	None	N
I/M	0.3227	likely_benign	0.25	benign	-1.316	Destabilizing	0.064	N	0.675	prob.neutral	N	0.50419234	None	None	N
I/N	0.9767	likely_pathogenic	0.9534	pathogenic	-2.754	Highly Destabilizing	0.995	D	0.819	deleterious	N	0.515802135	None	None	N
I/P	0.9975	likely_pathogenic	0.9952	pathogenic	-1.74	Destabilizing	0.997	D	0.81	deleterious	None	None	None	None	N
I/Q	0.9922	likely_pathogenic	0.9852	pathogenic	-2.516	Highly Destabilizing	0.992	D	0.833	deleterious	None	None	None	None	N
I/R	0.9929	likely_pathogenic	0.9869	pathogenic	-2.014	Highly Destabilizing	0.991	D	0.82	deleterious	None	None	None	None	N
I/S	0.9041	likely_pathogenic	0.8295	pathogenic	-3.318	Highly Destabilizing	0.335	N	0.7	prob.neutral	N	0.48854362	None	None	N
I/T	0.867	likely_pathogenic	0.7277	pathogenic	-2.912	Highly Destabilizing	0.004	N	0.501	neutral	N	0.492164471	None	None	N
I/V	0.1056	likely_benign	0.092	benign	-1.74	Destabilizing	None	N	0.259	neutral	N	0.427886588	None	None	N
I/W	0.9964	likely_pathogenic	0.994	pathogenic	-2.081	Highly Destabilizing	0.994	D	0.817	deleterious	None	None	None	None	N
I/Y	0.9838	likely_pathogenic	0.9767	pathogenic	-1.864	Destabilizing	0.307	N	0.783	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.