TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8906	26941;26942;26943	chr2:178713942;178713941;178713940	chr2:179578669;179578668;179578667
N2AB	8589	25990;25991;25992	chr2:178713942;178713941;178713940	chr2:179578669;179578668;179578667
N2A	7662	23209;23210;23211	chr2:178713942;178713941;178713940	chr2:179578669;179578668;179578667
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: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-74
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1557
• 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
N/K	rs776901808	-0.497	1.0	D	0.709	0.486	0.195762928549	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
N/K	rs776901808	-0.497	1.0	D	0.709	0.486	0.195762928549	gnomAD-4.0.0	1.36856E-06	None	None	None	None	N	None	0	2.23714E-05	None	0	0	None	0	0	0	1.15958E-05	0
N/S	None	None	0.999	N	0.563	0.543	0.260249123532	gnomAD-4.0.0	1.59162E-06	None	None	None	None	N	None	0	0	None	4.76735E-05	0	None	0	0	0	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
N/A	0.9884	likely_pathogenic	0.989	pathogenic	-0.849	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
N/C	0.9616	likely_pathogenic	0.9699	pathogenic	-0.327	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
N/D	0.9617	likely_pathogenic	0.9582	pathogenic	-1.393	Destabilizing	0.999	D	0.593	neutral	D	0.540738066	None	None	N
N/E	0.9947	likely_pathogenic	0.9942	pathogenic	-1.318	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
N/F	0.9979	likely_pathogenic	0.9975	pathogenic	-0.897	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
N/G	0.9479	likely_pathogenic	0.9481	pathogenic	-1.121	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
N/H	0.9375	likely_pathogenic	0.9425	pathogenic	-0.936	Destabilizing	1.0	D	0.723	prob.delet.	D	0.530484624	None	None	N
N/I	0.9787	likely_pathogenic	0.9756	pathogenic	-0.176	Destabilizing	1.0	D	0.723	prob.delet.	D	0.535511053	None	None	N
N/K	0.9947	likely_pathogenic	0.994	pathogenic	-0.213	Destabilizing	1.0	D	0.709	prob.delet.	D	0.55285484	None	None	N
N/L	0.9694	likely_pathogenic	0.9612	pathogenic	-0.176	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
N/M	0.9811	likely_pathogenic	0.9783	pathogenic	0.326	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
N/P	0.9962	likely_pathogenic	0.9961	pathogenic	-0.374	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
N/Q	0.9945	likely_pathogenic	0.9947	pathogenic	-1.094	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
N/R	0.9963	likely_pathogenic	0.9961	pathogenic	-0.06	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
N/S	0.6887	likely_pathogenic	0.7226	pathogenic	-0.853	Destabilizing	0.999	D	0.563	neutral	N	0.493475965	None	None	N
N/T	0.9008	likely_pathogenic	0.896	pathogenic	-0.62	Destabilizing	0.999	D	0.675	prob.neutral	N	0.49540175	None	None	N
N/V	0.9823	likely_pathogenic	0.9806	pathogenic	-0.374	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
N/W	0.9996	likely_pathogenic	0.9996	pathogenic	-0.697	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
N/Y	0.9772	likely_pathogenic	0.9753	pathogenic	-0.407	Destabilizing	1.0	D	0.738	prob.delet.	D	0.535257564	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.