TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6216	18871;18872;18873	chr2:178729510;178729509;178729508	chr2:179594237;179594236;179594235
N2AB	5899	17920;17921;17922	chr2:178729510;178729509;178729508	chr2:179594237;179594236;179594235
N2A	4972	15139;15140;15141	chr2:178729510;178729509;178729508	chr2:179594237;179594236;179594235
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-46
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1637
• 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	rs369242073	-0.734	0.999	N	0.665	0.273	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	3.27E-05	None	0	0	0
V/M	rs369242073	-0.734	0.999	N	0.665	0.273	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
V/M	rs369242073	-0.734	0.999	N	0.665	0.273	None	gnomAD-4.0.0	1.54952E-05	None	None	None	None	N	None	6.67682E-05	0	None	0	0	None	0	0	1.18681E-05	2.19621E-05	6.40533E-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
V/A	0.0979	likely_benign	0.1095	benign	-2.174	Highly Destabilizing	0.004	N	0.215	neutral	N	0.436758708	None	None	N
V/C	0.714	likely_pathogenic	0.7505	pathogenic	-1.457	Destabilizing	0.997	D	0.751	deleterious	None	None	None	None	N
V/D	0.7121	likely_pathogenic	0.8375	pathogenic	-2.401	Highly Destabilizing	0.988	D	0.808	deleterious	None	None	None	None	N
V/E	0.6211	likely_pathogenic	0.7525	pathogenic	-2.315	Highly Destabilizing	0.968	D	0.757	deleterious	N	0.516608833	None	None	N
V/F	0.2846	likely_benign	0.3569	ambiguous	-1.549	Destabilizing	0.988	D	0.799	deleterious	None	None	None	None	N
V/G	0.2708	likely_benign	0.3353	benign	-2.601	Highly Destabilizing	0.811	D	0.716	prob.delet.	N	0.490110787	None	None	N
V/H	0.8396	likely_pathogenic	0.9044	pathogenic	-2.197	Highly Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
V/I	0.0844	likely_benign	0.0929	benign	-1.034	Destabilizing	0.825	D	0.605	neutral	None	None	None	None	N
V/K	0.6898	likely_pathogenic	0.8004	pathogenic	-1.933	Destabilizing	0.976	D	0.764	deleterious	None	None	None	None	N
V/L	0.2271	likely_benign	0.2913	benign	-1.034	Destabilizing	0.9	D	0.573	neutral	N	0.474738306	None	None	N
V/M	0.1429	likely_benign	0.1754	benign	-0.724	Destabilizing	0.999	D	0.665	neutral	N	0.477019735	None	None	N
V/N	0.6025	likely_pathogenic	0.7304	pathogenic	-1.827	Destabilizing	0.988	D	0.822	deleterious	None	None	None	None	N
V/P	0.8976	likely_pathogenic	0.938	pathogenic	-1.384	Destabilizing	0.988	D	0.771	deleterious	None	None	None	None	N
V/Q	0.6432	likely_pathogenic	0.7507	pathogenic	-1.895	Destabilizing	0.988	D	0.784	deleterious	None	None	None	None	N
V/R	0.6128	likely_pathogenic	0.7327	pathogenic	-1.433	Destabilizing	0.988	D	0.821	deleterious	None	None	None	None	N
V/S	0.2738	likely_benign	0.3485	ambiguous	-2.381	Highly Destabilizing	0.851	D	0.679	prob.neutral	None	None	None	None	N
V/T	0.1321	likely_benign	0.164	benign	-2.177	Highly Destabilizing	0.919	D	0.618	neutral	None	None	None	None	N
V/W	0.9048	likely_pathogenic	0.9444	pathogenic	-1.882	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
V/Y	0.753	likely_pathogenic	0.8204	pathogenic	-1.617	Destabilizing	0.996	D	0.773	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.