TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32182	96769;96770;96771	chr2:178543429;178543428;178543427	chr2:179408156;179408155;179408154
N2AB	30541	91846;91847;91848	chr2:178543429;178543428;178543427	chr2:179408156;179408155;179408154
N2A	29614	89065;89066;89067	chr2:178543429;178543428;178543427	chr2:179408156;179408155;179408154
N2B	23117	69574;69575;69576	chr2:178543429;178543428;178543427	chr2:179408156;179408155;179408154
Novex-1	23242	69949;69950;69951	chr2:178543429;178543428;178543427	chr2:179408156;179408155;179408154
Novex-2	23309	70150;70151;70152	chr2:178543429;178543428;178543427	chr2:179408156;179408155;179408154
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-122
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.2714
• 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
E/G	rs1311963909	-1.137	1.0	N	0.77	0.59	0.461759001683	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/G	rs1311963909	-1.137	1.0	N	0.77	0.59	0.461759001683	gnomAD-4.0.0	5.47381E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19581E-06	0	0
E/K	None	None	0.998	N	0.552	0.378	0.366659145958	gnomAD-4.0.0	2.05275E-06	None	None	None	None	I	None	0	0	None	0	2.52169E-05	None	0	0	8.99504E-07	0	1.65695E-05

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
E/A	0.5616	ambiguous	0.5413	ambiguous	-1.072	Destabilizing	0.997	D	0.684	prob.neutral	N	0.501413194	None	None	I
E/C	0.9392	likely_pathogenic	0.936	pathogenic	-0.911	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
E/D	0.9108	likely_pathogenic	0.8887	pathogenic	-1.614	Destabilizing	0.974	D	0.461	neutral	N	0.512021066	None	None	I
E/F	0.9872	likely_pathogenic	0.9816	pathogenic	-1.256	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
E/G	0.7482	likely_pathogenic	0.73	pathogenic	-1.421	Destabilizing	1.0	D	0.77	deleterious	N	0.500664761	None	None	I
E/H	0.9567	likely_pathogenic	0.9417	pathogenic	-1.471	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/I	0.7822	likely_pathogenic	0.7428	pathogenic	-0.11	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	I
E/K	0.6814	likely_pathogenic	0.6129	pathogenic	-1.33	Destabilizing	0.998	D	0.552	neutral	N	0.468873569	None	None	I
E/L	0.9196	likely_pathogenic	0.8937	pathogenic	-0.11	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	I
E/M	0.8411	likely_pathogenic	0.8118	pathogenic	0.431	Stabilizing	0.999	D	0.84	deleterious	None	None	None	None	I
E/N	0.9274	likely_pathogenic	0.9103	pathogenic	-1.541	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	I
E/P	0.9983	likely_pathogenic	0.9981	pathogenic	-0.411	Destabilizing	0.994	D	0.834	deleterious	None	None	None	None	I
E/Q	0.3385	likely_benign	0.295	benign	-1.316	Destabilizing	0.999	D	0.633	neutral	D	0.52313526	None	None	I
E/R	0.7969	likely_pathogenic	0.7453	pathogenic	-1.3	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
E/S	0.6975	likely_pathogenic	0.6727	pathogenic	-2.057	Highly Destabilizing	0.997	D	0.615	neutral	None	None	None	None	I
E/T	0.7735	likely_pathogenic	0.7347	pathogenic	-1.736	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	I
E/V	0.499	ambiguous	0.4535	ambiguous	-0.411	Destabilizing	0.998	D	0.834	deleterious	N	0.448034495	None	None	I
E/W	0.9972	likely_pathogenic	0.9954	pathogenic	-1.454	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
E/Y	0.9808	likely_pathogenic	0.9747	pathogenic	-1.118	Destabilizing	1.0	D	0.854	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.