TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27605	83038;83039;83040	chr2:178563319;178563318;178563317	chr2:179428046;179428045;179428044
N2AB	25964	78115;78116;78117	chr2:178563319;178563318;178563317	chr2:179428046;179428045;179428044
N2A	25037	75334;75335;75336	chr2:178563319;178563318;178563317	chr2:179428046;179428045;179428044
N2B	18540	55843;55844;55845	chr2:178563319;178563318;178563317	chr2:179428046;179428045;179428044
Novex-1	18665	56218;56219;56220	chr2:178563319;178563318;178563317	chr2:179428046;179428045;179428044
Novex-2	18732	56419;56420;56421	chr2:178563319;178563318;178563317	chr2:179428046;179428045;179428044
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-89
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1211
• 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
Y/C	rs753352392	-1.929	1.0	D	0.868	0.882	0.888010141456	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	2.9E-05	None	0	1.11919E-04	None	0	None	0	8.92E-06	0
Y/C	rs753352392	-1.929	1.0	D	0.868	0.882	0.888010141456	gnomAD-4.0.0	6.36645E-06	None	None	None	None	N	None	0	2.28718E-05	None	0	5.5571E-05	None	0	0	2.85871E-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
Y/A	0.9939	likely_pathogenic	0.9943	pathogenic	-3.441	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
Y/C	0.8776	likely_pathogenic	0.8804	pathogenic	-1.801	Destabilizing	1.0	D	0.868	deleterious	D	0.666513903	None	None	N
Y/D	0.9939	likely_pathogenic	0.9942	pathogenic	-3.756	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.666715707	None	None	N
Y/E	0.9982	likely_pathogenic	0.9983	pathogenic	-3.533	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/F	0.1987	likely_benign	0.1973	benign	-1.358	Destabilizing	0.999	D	0.658	neutral	D	0.55280502	None	None	N
Y/G	0.9879	likely_pathogenic	0.9888	pathogenic	-3.854	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
Y/H	0.9673	likely_pathogenic	0.9674	pathogenic	-2.535	Highly Destabilizing	1.0	D	0.825	deleterious	D	0.640572182	None	None	N
Y/I	0.9603	likely_pathogenic	0.9618	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/K	0.9985	likely_pathogenic	0.9986	pathogenic	-2.359	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/L	0.9352	likely_pathogenic	0.9361	pathogenic	-2.042	Highly Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
Y/M	0.9742	likely_pathogenic	0.9745	pathogenic	-1.752	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/N	0.9652	likely_pathogenic	0.9664	pathogenic	-3.164	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.666513903	None	None	N
Y/P	0.9987	likely_pathogenic	0.9988	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	N
Y/Q	0.9974	likely_pathogenic	0.9976	pathogenic	-2.895	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.9941	likely_pathogenic	0.9945	pathogenic	-2.167	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/S	0.9767	likely_pathogenic	0.9779	pathogenic	-3.473	Highly Destabilizing	1.0	D	0.901	deleterious	D	0.640975791	None	None	N
Y/T	0.9918	likely_pathogenic	0.9923	pathogenic	-3.129	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/V	0.9403	likely_pathogenic	0.941	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
Y/W	0.7318	likely_pathogenic	0.728	pathogenic	-0.552	Destabilizing	1.0	D	0.799	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.