TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26342	79249;79250;79251	chr2:178567108;178567107;178567106	chr2:179431835;179431834;179431833
N2AB	24701	74326;74327;74328	chr2:178567108;178567107;178567106	chr2:179431835;179431834;179431833
N2A	23774	71545;71546;71547	chr2:178567108;178567107;178567106	chr2:179431835;179431834;179431833
N2B	17277	52054;52055;52056	chr2:178567108;178567107;178567106	chr2:179431835;179431834;179431833
Novex-1	17402	52429;52430;52431	chr2:178567108;178567107;178567106	chr2:179431835;179431834;179431833
Novex-2	17469	52630;52631;52632	chr2:178567108;178567107;178567106	chr2:179431835;179431834;179431833
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: Fn3-79
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.7303
• 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/E	None	None	0.983	N	0.547	0.449	0.572556545866	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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	0.1056	likely_benign	0.1101	benign	-0.671	Destabilizing	0.892	D	0.456	neutral	N	0.421298971	None	None	I
V/C	0.5777	likely_pathogenic	0.6082	pathogenic	-0.743	Destabilizing	0.999	D	0.56	neutral	None	None	None	None	I
V/D	0.2876	likely_benign	0.3017	benign	-0.274	Destabilizing	0.996	D	0.584	neutral	None	None	None	None	I
V/E	0.1991	likely_benign	0.2187	benign	-0.352	Destabilizing	0.983	D	0.547	neutral	N	0.389783986	None	None	I
V/F	0.135	likely_benign	0.1364	benign	-0.658	Destabilizing	0.975	D	0.568	neutral	None	None	None	None	I
V/G	0.1238	likely_benign	0.1327	benign	-0.853	Destabilizing	0.983	D	0.582	neutral	N	0.431150606	None	None	I
V/H	0.3827	ambiguous	0.4172	ambiguous	-0.276	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	I
V/I	0.0706	likely_benign	0.0684	benign	-0.327	Destabilizing	0.693	D	0.427	neutral	None	None	None	None	I
V/K	0.199	likely_benign	0.2251	benign	-0.613	Destabilizing	0.987	D	0.548	neutral	None	None	None	None	I
V/L	0.1117	likely_benign	0.1109	benign	-0.327	Destabilizing	0.011	N	0.177	neutral	N	0.448640288	None	None	I
V/M	0.0947	likely_benign	0.0987	benign	-0.423	Destabilizing	0.967	D	0.525	neutral	N	0.44558134	None	None	I
V/N	0.1573	likely_benign	0.1706	benign	-0.44	Destabilizing	0.996	D	0.583	neutral	None	None	None	None	I
V/P	0.2179	likely_benign	0.2046	benign	-0.406	Destabilizing	0.996	D	0.537	neutral	None	None	None	None	I
V/Q	0.1757	likely_benign	0.1962	benign	-0.633	Destabilizing	0.996	D	0.541	neutral	None	None	None	None	I
V/R	0.2146	likely_benign	0.2454	benign	-0.088	Destabilizing	0.987	D	0.584	neutral	None	None	None	None	I
V/S	0.124	likely_benign	0.1309	benign	-0.866	Destabilizing	0.987	D	0.547	neutral	None	None	None	None	I
V/T	0.1107	likely_benign	0.1181	benign	-0.836	Destabilizing	0.916	D	0.491	neutral	None	None	None	None	I
V/W	0.6882	likely_pathogenic	0.7086	pathogenic	-0.749	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	I
V/Y	0.4215	ambiguous	0.4258	ambiguous	-0.464	Destabilizing	0.987	D	0.557	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.