TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35779	107560;107561;107562	chr2:178528316;178528315;178528314	chr2:179393043;179393042;179393041
N2AB	34138	102637;102638;102639	chr2:178528316;178528315;178528314	chr2:179393043;179393042;179393041
N2A	33211	99856;99857;99858	chr2:178528316;178528315;178528314	chr2:179393043;179393042;179393041
N2B	26714	80365;80366;80367	chr2:178528316;178528315;178528314	chr2:179393043;179393042;179393041
Novex-1	26839	80740;80741;80742	chr2:178528316;178528315;178528314	chr2:179393043;179393042;179393041
Novex-2	26906	80941;80942;80943	chr2:178528316;178528315;178528314	chr2:179393043;179393042;179393041
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-168
• Domain position: 78
• Structural Position: 162
• Q(SASA): 1.0743
• 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
F/V	None	None	0.425	N	0.275	0.241	0.45563089846	gnomAD-4.0.0	3.18219E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71585E-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
F/A	0.5791	likely_pathogenic	0.5308	ambiguous	-0.829	Destabilizing	0.495	N	0.283	neutral	None	None	None	None	I
F/C	0.5454	ambiguous	0.5584	ambiguous	-0.384	Destabilizing	0.993	D	0.244	neutral	N	0.441533463	None	None	I
F/D	0.7633	likely_pathogenic	0.7525	pathogenic	0.616	Stabilizing	0.543	D	0.271	neutral	None	None	None	None	I
F/E	0.823	likely_pathogenic	0.7965	pathogenic	0.589	Stabilizing	0.013	N	0.218	neutral	None	None	None	None	I
F/G	0.7954	likely_pathogenic	0.7699	pathogenic	-0.996	Destabilizing	0.828	D	0.26	neutral	None	None	None	None	I
F/H	0.5675	likely_pathogenic	0.5335	ambiguous	0.254	Stabilizing	0.893	D	0.274	neutral	None	None	None	None	I
F/I	0.2184	likely_benign	0.2029	benign	-0.418	Destabilizing	0.642	D	0.313	neutral	N	0.370441369	None	None	I
F/K	0.8292	likely_pathogenic	0.8115	pathogenic	-0.123	Destabilizing	0.013	N	0.171	neutral	None	None	None	None	I
F/L	0.8091	likely_pathogenic	0.7826	pathogenic	-0.418	Destabilizing	0.27	N	0.291	neutral	N	0.40107092	None	None	I
F/M	0.5754	likely_pathogenic	0.5393	ambiguous	-0.451	Destabilizing	0.981	D	0.279	neutral	None	None	None	None	I
F/N	0.6239	likely_pathogenic	0.5967	pathogenic	-0.14	Destabilizing	0.828	D	0.312	neutral	None	None	None	None	I
F/P	0.9066	likely_pathogenic	0.8988	pathogenic	-0.537	Destabilizing	0.936	D	0.273	neutral	None	None	None	None	I
F/Q	0.7616	likely_pathogenic	0.7221	pathogenic	-0.164	Destabilizing	0.085	N	0.256	neutral	None	None	None	None	I
F/R	0.7144	likely_pathogenic	0.6894	pathogenic	0.262	Stabilizing	0.543	D	0.329	neutral	None	None	None	None	I
F/S	0.4023	ambiguous	0.3541	ambiguous	-0.736	Destabilizing	0.27	N	0.248	neutral	N	0.328839888	None	None	I
F/T	0.5203	ambiguous	0.4754	ambiguous	-0.671	Destabilizing	0.031	N	0.232	neutral	None	None	None	None	I
F/V	0.2534	likely_benign	0.2283	benign	-0.537	Destabilizing	0.425	N	0.275	neutral	N	0.369902651	None	None	I
F/W	0.6537	likely_pathogenic	0.6361	pathogenic	-0.358	Destabilizing	0.944	D	0.318	neutral	None	None	None	None	I
F/Y	0.1837	likely_benign	0.1772	benign	-0.324	Destabilizing	0.006	N	0.321	neutral	N	0.441186746	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.