TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5433	16522;16523;16524	chr2:178732879;178732878;178732877	chr2:179597606;179597605;179597604
N2AB	5116	15571;15572;15573	chr2:178732879;178732878;178732877	chr2:179597606;179597605;179597604
N2A	4189	12790;12791;12792	chr2:178732879;178732878;178732877	chr2:179597606;179597605;179597604
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-37
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1459
• 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
N/D	rs749623638	-1.882	0.999	D	0.591	0.544	0.336155897331	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.66E-05	0	0
N/D	rs749623638	-1.882	0.999	D	0.591	0.544	0.336155897331	gnomAD-4.0.0	6.00161E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	0	7.32654E-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
N/A	0.9835	likely_pathogenic	0.9857	pathogenic	-0.531	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
N/C	0.9566	likely_pathogenic	0.9635	pathogenic	0.042	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
N/D	0.9554	likely_pathogenic	0.9593	pathogenic	-1.277	Destabilizing	0.999	D	0.591	neutral	D	0.541890155	None	None	I
N/E	0.9978	likely_pathogenic	0.9979	pathogenic	-1.247	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	I
N/F	0.999	likely_pathogenic	0.999	pathogenic	-0.78	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
N/G	0.9627	likely_pathogenic	0.9686	pathogenic	-0.77	Destabilizing	0.999	D	0.53	neutral	None	None	None	None	I
N/H	0.9626	likely_pathogenic	0.9651	pathogenic	-0.817	Destabilizing	1.0	D	0.723	prob.delet.	D	0.525217931	None	None	I
N/I	0.9912	likely_pathogenic	0.9916	pathogenic	0.037	Stabilizing	1.0	D	0.716	prob.delet.	D	0.554931981	None	None	I
N/K	0.9977	likely_pathogenic	0.9977	pathogenic	-0.091	Destabilizing	1.0	D	0.705	prob.neutral	D	0.542650623	None	None	I
N/L	0.981	likely_pathogenic	0.98	pathogenic	0.037	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
N/M	0.9926	likely_pathogenic	0.9934	pathogenic	0.675	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
N/P	0.9948	likely_pathogenic	0.9947	pathogenic	-0.125	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
N/Q	0.9971	likely_pathogenic	0.9973	pathogenic	-0.977	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
N/R	0.9957	likely_pathogenic	0.9954	pathogenic	0.067	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
N/S	0.5319	ambiguous	0.5866	pathogenic	-0.57	Destabilizing	0.999	D	0.559	neutral	N	0.500059331	None	None	I
N/T	0.8981	likely_pathogenic	0.9097	pathogenic	-0.395	Destabilizing	0.999	D	0.672	neutral	N	0.521570627	None	None	I
N/V	0.984	likely_pathogenic	0.9851	pathogenic	-0.125	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
N/W	0.9997	likely_pathogenic	0.9997	pathogenic	-0.661	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
N/Y	0.9889	likely_pathogenic	0.989	pathogenic	-0.345	Destabilizing	1.0	D	0.731	prob.delet.	D	0.554678492	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.