TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10049	30370;30371;30372	chr2:178704225;178704224;178704223	chr2:179568952;179568951;179568950
N2AB	9732	29419;29420;29421	chr2:178704225;178704224;178704223	chr2:179568952;179568951;179568950
N2A	8805	26638;26639;26640	chr2:178704225;178704224;178704223	chr2:179568952;179568951;179568950
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-85
• Domain position: 61
• Structural Position: 143
• Q(SASA): 0.132
• 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
D/G	rs2075487390	None	0.919	None	0.595	0.298	0.18274738541	gnomAD-4.0.0	2.05243E-06	None	None	None	None	N	None	2.98686E-05	0	None	0	0	None	0	0	1.7988E-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
D/A	0.735	likely_pathogenic	0.4957	ambiguous	-0.422	Destabilizing	0.988	D	0.684	prob.neutral	None	None	None	None	N
D/C	0.9816	likely_pathogenic	0.9398	pathogenic	0.011	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
D/E	0.6837	likely_pathogenic	0.4486	ambiguous	-0.674	Destabilizing	0.958	D	0.559	neutral	None	None	None	None	N
D/F	0.9609	likely_pathogenic	0.8923	pathogenic	-0.626	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
D/G	0.6616	likely_pathogenic	0.4009	ambiguous	-0.662	Destabilizing	0.919	D	0.595	neutral	None	None	None	None	N
D/H	0.8647	likely_pathogenic	0.6663	pathogenic	-0.872	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
D/I	0.9685	likely_pathogenic	0.908	pathogenic	0.174	Stabilizing	0.995	D	0.775	deleterious	None	None	None	None	N
D/K	0.9299	likely_pathogenic	0.7957	pathogenic	-0.072	Destabilizing	0.991	D	0.677	prob.neutral	None	None	None	None	N
D/L	0.9314	likely_pathogenic	0.8377	pathogenic	0.174	Stabilizing	0.995	D	0.767	deleterious	None	None	None	None	N
D/M	0.9783	likely_pathogenic	0.9366	pathogenic	0.598	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
D/N	0.3143	likely_benign	0.1607	benign	-0.281	Destabilizing	0.067	N	0.341	neutral	None	None	None	None	N
D/P	0.9915	likely_pathogenic	0.9727	pathogenic	-0.001	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
D/Q	0.9067	likely_pathogenic	0.7574	pathogenic	-0.264	Destabilizing	0.991	D	0.733	prob.delet.	None	None	None	None	N
D/R	0.9193	likely_pathogenic	0.7932	pathogenic	-0.069	Destabilizing	0.991	D	0.757	deleterious	None	None	None	None	N
D/S	0.5601	ambiguous	0.3241	benign	-0.456	Destabilizing	0.938	D	0.593	neutral	None	None	None	None	N
D/T	0.8737	likely_pathogenic	0.7026	pathogenic	-0.274	Destabilizing	0.991	D	0.681	prob.neutral	None	None	None	None	N
D/V	0.903	likely_pathogenic	0.7708	pathogenic	-0.001	Destabilizing	0.994	D	0.771	deleterious	None	None	None	None	N
D/W	0.9925	likely_pathogenic	0.9792	pathogenic	-0.593	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
D/Y	0.7781	likely_pathogenic	0.5726	pathogenic	-0.419	Destabilizing	0.999	D	0.781	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.