TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20332	61219;61220;61221	chr2:178590731;178590730;178590729	chr2:179455458;179455457;179455456
N2AB	18691	56296;56297;56298	chr2:178590731;178590730;178590729	chr2:179455458;179455457;179455456
N2A	17764	53515;53516;53517	chr2:178590731;178590730;178590729	chr2:179455458;179455457;179455456
N2B	11267	34024;34025;34026	chr2:178590731;178590730;178590729	chr2:179455458;179455457;179455456
Novex-1	11392	34399;34400;34401	chr2:178590731;178590730;178590729	chr2:179455458;179455457;179455456
Novex-2	11459	34600;34601;34602	chr2:178590731;178590730;178590729	chr2:179455458;179455457;179455456
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: Fn3-35
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.1031
• 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
V/M	rs961573875	-0.333	0.997	N	0.693	0.395	0.570128362464	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	4.41E-05	0	0
V/M	rs961573875	-0.333	0.997	N	0.693	0.395	0.570128362464	gnomAD-4.0.0	5.58301E-06	None	None	None	None	N	None	1.33576E-05	0	None	0	0	None	0	0	6.78608E-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	0.3387	likely_benign	0.3281	benign	-1.855	Destabilizing	0.02	N	0.307	neutral	D	0.527741364	None	None	N
V/C	0.8327	likely_pathogenic	0.8207	pathogenic	-1.424	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
V/D	0.9728	likely_pathogenic	0.961	pathogenic	-2.211	Highly Destabilizing	0.993	D	0.867	deleterious	None	None	None	None	N
V/E	0.9349	likely_pathogenic	0.9225	pathogenic	-1.971	Destabilizing	0.982	D	0.831	deleterious	D	0.532414089	None	None	N
V/F	0.6708	likely_pathogenic	0.677	pathogenic	-1.104	Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	N
V/G	0.6953	likely_pathogenic	0.6416	pathogenic	-2.411	Highly Destabilizing	0.885	D	0.802	deleterious	D	0.543934979	None	None	N
V/H	0.9792	likely_pathogenic	0.9775	pathogenic	-2.124	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
V/I	0.1145	likely_benign	0.1328	benign	-0.304	Destabilizing	0.893	D	0.547	neutral	None	None	None	None	N
V/K	0.975	likely_pathogenic	0.9698	pathogenic	-1.504	Destabilizing	0.986	D	0.843	deleterious	None	None	None	None	N
V/L	0.5407	ambiguous	0.5792	pathogenic	-0.304	Destabilizing	0.863	D	0.66	neutral	N	0.51622793	None	None	N
V/M	0.4345	ambiguous	0.4943	ambiguous	-0.385	Destabilizing	0.997	D	0.693	prob.neutral	N	0.513802855	None	None	N
V/N	0.9103	likely_pathogenic	0.8961	pathogenic	-1.858	Destabilizing	0.993	D	0.859	deleterious	None	None	None	None	N
V/P	0.9735	likely_pathogenic	0.9608	pathogenic	-0.793	Destabilizing	0.993	D	0.851	deleterious	None	None	None	None	N
V/Q	0.9344	likely_pathogenic	0.9286	pathogenic	-1.648	Destabilizing	0.993	D	0.841	deleterious	None	None	None	None	N
V/R	0.9684	likely_pathogenic	0.9583	pathogenic	-1.472	Destabilizing	0.993	D	0.857	deleterious	None	None	None	None	N
V/S	0.6373	likely_pathogenic	0.5922	pathogenic	-2.515	Highly Destabilizing	0.91	D	0.783	deleterious	None	None	None	None	N
V/T	0.5227	ambiguous	0.5097	ambiguous	-2.108	Highly Destabilizing	0.953	D	0.665	neutral	None	None	None	None	N
V/W	0.9925	likely_pathogenic	0.9923	pathogenic	-1.561	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
V/Y	0.9559	likely_pathogenic	0.9519	pathogenic	-1.142	Destabilizing	0.998	D	0.779	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.