TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18616	56071;56072;56073	chr2:178601058;178601057;178601056	chr2:179465785;179465784;179465783
N2AB	16975	51148;51149;51150	chr2:178601058;178601057;178601056	chr2:179465785;179465784;179465783
N2A	16048	48367;48368;48369	chr2:178601058;178601057;178601056	chr2:179465785;179465784;179465783
N2B	9551	28876;28877;28878	chr2:178601058;178601057;178601056	chr2:179465785;179465784;179465783
Novex-1	9676	29251;29252;29253	chr2:178601058;178601057;178601056	chr2:179465785;179465784;179465783
Novex-2	9743	29452;29453;29454	chr2:178601058;178601057;178601056	chr2:179465785;179465784;179465783
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-23
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0934
• 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/A	rs2053304882	None	0.78	D	0.559	0.537	0.708570864396	gnomAD-4.0.0	1.5935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86228E-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	0.8544	likely_pathogenic	0.8623	pathogenic	-2.553	Highly Destabilizing	0.78	D	0.559	neutral	D	0.523043837	None	None	N
V/C	0.9717	likely_pathogenic	0.9709	pathogenic	-1.959	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
V/D	0.9978	likely_pathogenic	0.9988	pathogenic	-3.521	Highly Destabilizing	0.995	D	0.873	deleterious	D	0.53516061	None	None	N
V/E	0.9919	likely_pathogenic	0.995	pathogenic	-3.196	Highly Destabilizing	0.996	D	0.846	deleterious	None	None	None	None	N
V/F	0.9131	likely_pathogenic	0.9061	pathogenic	-1.418	Destabilizing	0.968	D	0.741	deleterious	D	0.534907121	None	None	N
V/G	0.9595	likely_pathogenic	0.9709	pathogenic	-3.152	Highly Destabilizing	0.995	D	0.857	deleterious	D	0.53516061	None	None	N
V/H	0.9981	likely_pathogenic	0.9985	pathogenic	-3.022	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
V/I	0.0842	likely_benign	0.0739	benign	-0.791	Destabilizing	0.011	N	0.173	neutral	N	0.420861828	None	None	N
V/K	0.993	likely_pathogenic	0.9958	pathogenic	-2.083	Highly Destabilizing	0.988	D	0.846	deleterious	None	None	None	None	N
V/L	0.4919	ambiguous	0.467	ambiguous	-0.791	Destabilizing	0.437	N	0.319	neutral	N	0.45976972	None	None	N
V/M	0.7116	likely_pathogenic	0.6823	pathogenic	-1.102	Destabilizing	0.976	D	0.623	neutral	None	None	None	None	N
V/N	0.9933	likely_pathogenic	0.9953	pathogenic	-2.811	Highly Destabilizing	0.996	D	0.893	deleterious	None	None	None	None	N
V/P	0.9865	likely_pathogenic	0.9902	pathogenic	-1.363	Destabilizing	0.996	D	0.855	deleterious	None	None	None	None	N
V/Q	0.9919	likely_pathogenic	0.9946	pathogenic	-2.429	Highly Destabilizing	0.996	D	0.88	deleterious	None	None	None	None	N
V/R	0.9859	likely_pathogenic	0.992	pathogenic	-2.183	Highly Destabilizing	0.996	D	0.889	deleterious	None	None	None	None	N
V/S	0.9712	likely_pathogenic	0.977	pathogenic	-3.278	Highly Destabilizing	0.988	D	0.808	deleterious	None	None	None	None	N
V/T	0.8648	likely_pathogenic	0.8786	pathogenic	-2.799	Highly Destabilizing	0.919	D	0.587	neutral	None	None	None	None	N
V/W	0.9981	likely_pathogenic	0.9981	pathogenic	-1.974	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
V/Y	0.9938	likely_pathogenic	0.9946	pathogenic	-1.726	Destabilizing	0.996	D	0.747	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.