TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27872	83839;83840;83841	chr2:178562518;178562517;178562516	chr2:179427245;179427244;179427243
N2AB	26231	78916;78917;78918	chr2:178562518;178562517;178562516	chr2:179427245;179427244;179427243
N2A	25304	76135;76136;76137	chr2:178562518;178562517;178562516	chr2:179427245;179427244;179427243
N2B	18807	56644;56645;56646	chr2:178562518;178562517;178562516	chr2:179427245;179427244;179427243
Novex-1	18932	57019;57020;57021	chr2:178562518;178562517;178562516	chr2:179427245;179427244;179427243
Novex-2	18999	57220;57221;57222	chr2:178562518;178562517;178562516	chr2:179427245;179427244;179427243
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-91
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3822
• 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
L/P	rs547274306	-1.098	1.0	N	0.859	0.586	0.850441581223	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
L/R	None	None	0.999	N	0.859	0.575	0.827110624128	gnomAD-4.0.0	1.37062E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.34039E-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
L/A	0.6656	likely_pathogenic	0.7008	pathogenic	-1.922	Destabilizing	0.993	D	0.597	neutral	None	None	None	None	I
L/C	0.8285	likely_pathogenic	0.8557	pathogenic	-1.243	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
L/D	0.9908	likely_pathogenic	0.9934	pathogenic	-1.54	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
L/E	0.9523	likely_pathogenic	0.9644	pathogenic	-1.435	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
L/F	0.5524	ambiguous	0.6053	pathogenic	-1.16	Destabilizing	0.997	D	0.727	prob.delet.	N	0.508685883	None	None	I
L/G	0.9481	likely_pathogenic	0.9572	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
L/H	0.8881	likely_pathogenic	0.915	pathogenic	-1.44	Destabilizing	1.0	D	0.843	deleterious	N	0.501148968	None	None	I
L/I	0.1547	likely_benign	0.1645	benign	-0.789	Destabilizing	0.396	N	0.531	neutral	N	0.463414953	None	None	I
L/K	0.9211	likely_pathogenic	0.9371	pathogenic	-1.452	Destabilizing	0.989	D	0.835	deleterious	None	None	None	None	I
L/M	0.2475	likely_benign	0.2686	benign	-0.666	Destabilizing	0.992	D	0.726	prob.delet.	None	None	None	None	I
L/N	0.9482	likely_pathogenic	0.9599	pathogenic	-1.523	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
L/P	0.8142	likely_pathogenic	0.8431	pathogenic	-1.139	Destabilizing	1.0	D	0.859	deleterious	N	0.47949954	None	None	I
L/Q	0.8613	likely_pathogenic	0.8869	pathogenic	-1.551	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	I
L/R	0.8582	likely_pathogenic	0.8842	pathogenic	-0.943	Destabilizing	0.999	D	0.859	deleterious	N	0.496287122	None	None	I
L/S	0.8968	likely_pathogenic	0.9161	pathogenic	-2.19	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
L/T	0.6876	likely_pathogenic	0.7239	pathogenic	-1.947	Destabilizing	0.993	D	0.75	deleterious	None	None	None	None	I
L/V	0.1277	likely_benign	0.1366	benign	-1.139	Destabilizing	0.053	N	0.214	neutral	N	0.417466445	None	None	I
L/W	0.8089	likely_pathogenic	0.8593	pathogenic	-1.329	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
L/Y	0.8774	likely_pathogenic	0.9017	pathogenic	-1.074	Destabilizing	0.993	D	0.823	deleterious	None	None	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.