TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25298	76117;76118;76119	chr2:178570240;178570239;178570238	chr2:179434967;179434966;179434965
N2AB	23657	71194;71195;71196	chr2:178570240;178570239;178570238	chr2:179434967;179434966;179434965
N2A	22730	68413;68414;68415	chr2:178570240;178570239;178570238	chr2:179434967;179434966;179434965
N2B	16233	48922;48923;48924	chr2:178570240;178570239;178570238	chr2:179434967;179434966;179434965
Novex-1	16358	49297;49298;49299	chr2:178570240;178570239;178570238	chr2:179434967;179434966;179434965
Novex-2	16425	49498;49499;49500	chr2:178570240;178570239;178570238	chr2:179434967;179434966;179434965
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-71
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.0834
• 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
A/P	None	None	1.0	N	0.739	0.311	0.487772906946	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	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
A/C	0.509	ambiguous	0.5933	pathogenic	-1.858	Destabilizing	1.0	D	0.721	deleterious	None	None	None	None	N
A/D	0.9905	likely_pathogenic	0.9941	pathogenic	-2.996	Highly Destabilizing	1.0	D	0.796	deleterious	D	0.526553696	None	None	N
A/E	0.9704	likely_pathogenic	0.9786	pathogenic	-2.841	Highly Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
A/F	0.7479	likely_pathogenic	0.8247	pathogenic	-0.817	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/G	0.497	ambiguous	0.5528	ambiguous	-1.61	Destabilizing	0.999	D	0.591	neutral	N	0.499295181	None	None	N
A/H	0.9824	likely_pathogenic	0.9893	pathogenic	-1.735	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
A/I	0.377	ambiguous	0.4872	ambiguous	-0.248	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
A/K	0.9894	likely_pathogenic	0.9936	pathogenic	-1.346	Destabilizing	1.0	D	0.725	deleterious	None	None	None	None	N
A/L	0.3192	likely_benign	0.428	ambiguous	-0.248	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
A/M	0.2705	likely_benign	0.3326	benign	-0.791	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
A/N	0.946	likely_pathogenic	0.9643	pathogenic	-1.736	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
A/P	0.7143	likely_pathogenic	0.8045	pathogenic	-0.539	Destabilizing	1.0	D	0.739	deleterious	N	0.487938876	None	None	N
A/Q	0.9235	likely_pathogenic	0.9469	pathogenic	-1.646	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
A/R	0.9716	likely_pathogenic	0.9814	pathogenic	-1.304	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
A/S	0.2754	likely_benign	0.3016	benign	-2.026	Highly Destabilizing	0.999	D	0.632	neutral	N	0.507093088	None	None	N
A/T	0.3883	ambiguous	0.4256	ambiguous	-1.77	Destabilizing	1.0	D	0.729	deleterious	N	0.516438574	None	None	N
A/V	0.2235	likely_benign	0.2811	benign	-0.539	Destabilizing	0.999	D	0.661	prob.neutral	N	0.501717051	None	None	N
A/W	0.9827	likely_pathogenic	0.9904	pathogenic	-1.456	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
A/Y	0.9514	likely_pathogenic	0.9705	pathogenic	-1.004	Destabilizing	1.0	D	0.809	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.