TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31523	94792;94793;94794	chr2:178546861;178546860;178546859	chr2:179411588;179411587;179411586
N2AB	29882	89869;89870;89871	chr2:178546861;178546860;178546859	chr2:179411588;179411587;179411586
N2A	28955	87088;87089;87090	chr2:178546861;178546860;178546859	chr2:179411588;179411587;179411586
N2B	22458	67597;67598;67599	chr2:178546861;178546860;178546859	chr2:179411588;179411587;179411586
Novex-1	22583	67972;67973;67974	chr2:178546861;178546860;178546859	chr2:179411588;179411587;179411586
Novex-2	22650	68173;68174;68175	chr2:178546861;178546860;178546859	chr2:179411588;179411587;179411586
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-118
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0736
• 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	None	None	0.543	N	0.308	0.208	0.504907739247	gnomAD-4.0.0	1.62656E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45607E-05	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	0.6085	likely_pathogenic	0.4637	ambiguous	-2.363	Highly Destabilizing	0.543	D	0.308	neutral	N	0.501127979	None	None	N
V/C	0.9407	likely_pathogenic	0.9294	pathogenic	-2.585	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/D	0.9996	likely_pathogenic	0.9993	pathogenic	-2.997	Highly Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
V/E	0.998	likely_pathogenic	0.997	pathogenic	-2.751	Highly Destabilizing	0.998	D	0.869	deleterious	D	0.539665337	None	None	N
V/F	0.9611	likely_pathogenic	0.9605	pathogenic	-1.577	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
V/G	0.9569	likely_pathogenic	0.9301	pathogenic	-2.933	Highly Destabilizing	0.997	D	0.827	deleterious	D	0.533081971	None	None	N
V/H	0.9994	likely_pathogenic	0.9992	pathogenic	-2.667	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.1373	likely_benign	0.1489	benign	-0.753	Destabilizing	0.987	D	0.513	neutral	N	0.486115667	None	None	N
V/K	0.9986	likely_pathogenic	0.9981	pathogenic	-2.083	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
V/L	0.7772	likely_pathogenic	0.79	pathogenic	-0.753	Destabilizing	0.973	D	0.621	neutral	N	0.470746447	None	None	N
V/M	0.7972	likely_pathogenic	0.7893	pathogenic	-1.133	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/N	0.9977	likely_pathogenic	0.9964	pathogenic	-2.563	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/P	0.9994	likely_pathogenic	0.999	pathogenic	-1.264	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
V/Q	0.9964	likely_pathogenic	0.995	pathogenic	-2.358	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/R	0.996	likely_pathogenic	0.9946	pathogenic	-1.94	Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
V/S	0.9641	likely_pathogenic	0.9345	pathogenic	-3.251	Highly Destabilizing	0.995	D	0.852	deleterious	None	None	None	None	N
V/T	0.9019	likely_pathogenic	0.8431	pathogenic	-2.836	Highly Destabilizing	0.992	D	0.723	prob.delet.	None	None	None	None	N
V/W	0.9998	likely_pathogenic	0.9998	pathogenic	-2.011	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/Y	0.9974	likely_pathogenic	0.9971	pathogenic	-1.671	Destabilizing	1.0	D	0.857	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.