TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27921	83986;83987;83988	chr2:178562371;178562370;178562369	chr2:179427098;179427097;179427096
N2AB	26280	79063;79064;79065	chr2:178562371;178562370;178562369	chr2:179427098;179427097;179427096
N2A	25353	76282;76283;76284	chr2:178562371;178562370;178562369	chr2:179427098;179427097;179427096
N2B	18856	56791;56792;56793	chr2:178562371;178562370;178562369	chr2:179427098;179427097;179427096
Novex-1	18981	57166;57167;57168	chr2:178562371;178562370;178562369	chr2:179427098;179427097;179427096
Novex-2	19048	57367;57368;57369	chr2:178562371;178562370;178562369	chr2:179427098;179427097;179427096
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-91
• Domain position: 59
• Structural Position: 91
• Q(SASA): 0.1532
• 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/V	None	None	0.842	N	0.59	0.194	0.364342057095	gnomAD-4.0.0	1.60033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86867E-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
A/C	0.5727	likely_pathogenic	0.567	pathogenic	-0.704	Destabilizing	0.996	D	0.793	deleterious	None	None	None	None	N
A/D	0.8603	likely_pathogenic	0.8401	pathogenic	-1.132	Destabilizing	0.973	D	0.816	deleterious	None	None	None	None	N
A/E	0.8127	likely_pathogenic	0.7941	pathogenic	-1.038	Destabilizing	0.974	D	0.753	deleterious	N	0.520583122	None	None	N
A/F	0.685	likely_pathogenic	0.7021	pathogenic	-0.543	Destabilizing	0.996	D	0.881	deleterious	None	None	None	None	N
A/G	0.1737	likely_benign	0.1831	benign	-1.027	Destabilizing	0.426	N	0.569	neutral	N	0.472764817	None	None	N
A/H	0.8742	likely_pathogenic	0.8675	pathogenic	-1.401	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
A/I	0.6183	likely_pathogenic	0.6052	pathogenic	0.308	Stabilizing	0.985	D	0.804	deleterious	None	None	None	None	N
A/K	0.9217	likely_pathogenic	0.917	pathogenic	-0.816	Destabilizing	0.993	D	0.763	deleterious	None	None	None	None	N
A/L	0.545	ambiguous	0.5352	ambiguous	0.308	Stabilizing	0.95	D	0.662	neutral	None	None	None	None	N
A/M	0.4648	ambiguous	0.4705	ambiguous	0.106	Stabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
A/N	0.7205	likely_pathogenic	0.7266	pathogenic	-0.821	Destabilizing	0.806	D	0.831	deleterious	None	None	None	None	N
A/P	0.991	likely_pathogenic	0.9896	pathogenic	0.037	Stabilizing	0.982	D	0.798	deleterious	N	0.520583122	None	None	N
A/Q	0.8365	likely_pathogenic	0.8244	pathogenic	-0.766	Destabilizing	0.996	D	0.856	deleterious	None	None	None	None	N
A/R	0.9053	likely_pathogenic	0.9014	pathogenic	-0.814	Destabilizing	0.993	D	0.817	deleterious	None	None	None	None	N
A/S	0.1868	likely_benign	0.1856	benign	-1.255	Destabilizing	0.22	N	0.516	neutral	N	0.490615583	None	None	N
A/T	0.1515	likely_benign	0.1438	benign	-1.039	Destabilizing	0.035	N	0.404	neutral	N	0.492161779	None	None	N
A/V	0.3021	likely_benign	0.2862	benign	0.037	Stabilizing	0.842	D	0.59	neutral	N	0.482075284	None	None	N
A/W	0.954	likely_pathogenic	0.956	pathogenic	-1.145	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
A/Y	0.7846	likely_pathogenic	0.8088	pathogenic	-0.568	Destabilizing	0.999	D	0.879	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.