TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17187	51784;51785;51786	chr2:178609864;178609863;178609862	chr2:179474591;179474590;179474589
N2AB	15546	46861;46862;46863	chr2:178609864;178609863;178609862	chr2:179474591;179474590;179474589
N2A	14619	44080;44081;44082	chr2:178609864;178609863;178609862	chr2:179474591;179474590;179474589
N2B	8122	24589;24590;24591	chr2:178609864;178609863;178609862	chr2:179474591;179474590;179474589
Novex-1	8247	24964;24965;24966	chr2:178609864;178609863;178609862	chr2:179474591;179474590;179474589
Novex-2	8314	25165;25166;25167	chr2:178609864;178609863;178609862	chr2:179474591;179474590;179474589
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-13
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0522
• 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/M	None	None	0.009	N	0.175	0.025	0.315609569513	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
I/T	None	None	0.183	N	0.529	0.17	0.54848712621	gnomAD-4.0.0	1.36893E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99794E-07	1.15972E-05	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	0.3735	ambiguous	0.2947	benign	-2.417	Highly Destabilizing	0.114	N	0.504	neutral	None	None	None	None	N
I/C	0.7566	likely_pathogenic	0.6856	pathogenic	-1.524	Destabilizing	0.94	D	0.613	neutral	None	None	None	None	N
I/D	0.9545	likely_pathogenic	0.907	pathogenic	-3.027	Highly Destabilizing	0.418	N	0.657	neutral	None	None	None	None	N
I/E	0.7686	likely_pathogenic	0.6555	pathogenic	-2.78	Highly Destabilizing	0.129	N	0.573	neutral	None	None	None	None	N
I/F	0.3413	ambiguous	0.2653	benign	-1.317	Destabilizing	0.213	N	0.499	neutral	N	0.426494147	None	None	N
I/G	0.8362	likely_pathogenic	0.7452	pathogenic	-2.937	Highly Destabilizing	0.593	D	0.622	neutral	None	None	None	None	N
I/H	0.7925	likely_pathogenic	0.6865	pathogenic	-2.555	Highly Destabilizing	0.836	D	0.643	neutral	None	None	None	None	N
I/K	0.4692	ambiguous	0.3722	ambiguous	-1.662	Destabilizing	0.129	N	0.575	neutral	None	None	None	None	N
I/L	0.1562	likely_benign	0.123	benign	-0.885	Destabilizing	None	N	0.093	neutral	N	0.452024523	None	None	N
I/M	0.0884	likely_benign	0.0767	benign	-0.961	Destabilizing	0.009	N	0.175	neutral	N	0.442290319	None	None	N
I/N	0.6351	likely_pathogenic	0.4793	ambiguous	-2.087	Highly Destabilizing	0.523	D	0.689	prob.neutral	N	0.457662416	None	None	N
I/P	0.9879	likely_pathogenic	0.9773	pathogenic	-1.382	Destabilizing	0.816	D	0.693	prob.neutral	None	None	None	None	N
I/Q	0.5179	ambiguous	0.4163	ambiguous	-1.892	Destabilizing	0.012	N	0.455	neutral	None	None	None	None	N
I/R	0.4119	ambiguous	0.3131	benign	-1.522	Destabilizing	0.418	N	0.645	neutral	None	None	None	None	N
I/S	0.5404	ambiguous	0.4079	ambiguous	-2.653	Highly Destabilizing	0.183	N	0.546	neutral	N	0.426126001	None	None	N
I/T	0.2604	likely_benign	0.1956	benign	-2.279	Highly Destabilizing	0.183	N	0.529	neutral	N	0.433785479	None	None	N
I/V	0.1142	likely_benign	0.1009	benign	-1.382	Destabilizing	0.021	N	0.369	neutral	N	0.501029192	None	None	N
I/W	0.8983	likely_pathogenic	0.8562	pathogenic	-1.804	Destabilizing	0.983	D	0.625	neutral	None	None	None	None	N
I/Y	0.7271	likely_pathogenic	0.6268	pathogenic	-1.523	Destabilizing	0.593	D	0.654	neutral	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.