TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21249	63970;63971;63972	chr2:178587564;178587563;178587562	chr2:179452291;179452290;179452289
N2AB	19608	59047;59048;59049	chr2:178587564;178587563;178587562	chr2:179452291;179452290;179452289
N2A	18681	56266;56267;56268	chr2:178587564;178587563;178587562	chr2:179452291;179452290;179452289
N2B	12184	36775;36776;36777	chr2:178587564;178587563;178587562	chr2:179452291;179452290;179452289
Novex-1	12309	37150;37151;37152	chr2:178587564;178587563;178587562	chr2:179452291;179452290;179452289
Novex-2	12376	37351;37352;37353	chr2:178587564;178587563;178587562	chr2:179452291;179452290;179452289
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-123
• Domain position: 73
• Structural Position: 159
• Q(SASA): 0.2542
• 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
V/L	None	None	0.826	N	0.443	0.178	0.52540932818	gnomAD-4.0.0	1.36984E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79996E-06	0	0
V/M	None	None	0.996	N	0.475	0.275	0.610882576163	gnomAD-4.0.0	3.4246E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49989E-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
V/A	0.1461	likely_benign	0.1408	benign	-1.238	Destabilizing	0.509	D	0.357	neutral	N	0.441109388	None	None	I
V/C	0.5965	likely_pathogenic	0.6048	pathogenic	-0.873	Destabilizing	0.999	D	0.459	neutral	None	None	None	None	I
V/D	0.3252	likely_benign	0.2768	benign	-1.12	Destabilizing	0.939	D	0.563	neutral	None	None	None	None	I
V/E	0.1856	likely_benign	0.1644	benign	-1.189	Destabilizing	0.92	D	0.57	neutral	N	0.329189392	None	None	I
V/F	0.2133	likely_benign	0.2057	benign	-1.236	Destabilizing	0.997	D	0.468	neutral	None	None	None	None	I
V/G	0.2058	likely_benign	0.1968	benign	-1.469	Destabilizing	0.92	D	0.591	neutral	N	0.475819395	None	None	I
V/H	0.4234	ambiguous	0.4109	ambiguous	-1.02	Destabilizing	0.999	D	0.564	neutral	None	None	None	None	I
V/I	0.0898	likely_benign	0.0917	benign	-0.735	Destabilizing	0.863	D	0.421	neutral	None	None	None	None	I
V/K	0.2703	likely_benign	0.2332	benign	-0.949	Destabilizing	0.939	D	0.569	neutral	None	None	None	None	I
V/L	0.1752	likely_benign	0.179	benign	-0.735	Destabilizing	0.826	D	0.443	neutral	N	0.479723705	None	None	I
V/M	0.1511	likely_benign	0.1502	benign	-0.488	Destabilizing	0.996	D	0.475	neutral	N	0.487209824	None	None	I
V/N	0.2254	likely_benign	0.2113	benign	-0.675	Destabilizing	0.939	D	0.57	neutral	None	None	None	None	I
V/P	0.8951	likely_pathogenic	0.8858	pathogenic	-0.868	Destabilizing	0.991	D	0.55	neutral	None	None	None	None	I
V/Q	0.1976	likely_benign	0.1863	benign	-0.958	Destabilizing	0.991	D	0.556	neutral	None	None	None	None	I
V/R	0.2668	likely_benign	0.2276	benign	-0.37	Destabilizing	0.991	D	0.581	neutral	None	None	None	None	I
V/S	0.1447	likely_benign	0.1374	benign	-1.125	Destabilizing	0.2	N	0.302	neutral	None	None	None	None	I
V/T	0.1306	likely_benign	0.1279	benign	-1.096	Destabilizing	0.17	N	0.163	neutral	None	None	None	None	I
V/W	0.8068	likely_pathogenic	0.8021	pathogenic	-1.332	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
V/Y	0.5348	ambiguous	0.5215	ambiguous	-1.045	Destabilizing	0.997	D	0.462	neutral	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.