TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24863	74812;74813;74814	chr2:178571545;178571544;178571543	chr2:179436272;179436271;179436270
N2AB	23222	69889;69890;69891	chr2:178571545;178571544;178571543	chr2:179436272;179436271;179436270
N2A	22295	67108;67109;67110	chr2:178571545;178571544;178571543	chr2:179436272;179436271;179436270
N2B	15798	47617;47618;47619	chr2:178571545;178571544;178571543	chr2:179436272;179436271;179436270
Novex-1	15923	47992;47993;47994	chr2:178571545;178571544;178571543	chr2:179436272;179436271;179436270
Novex-2	15990	48193;48194;48195	chr2:178571545;178571544;178571543	chr2:179436272;179436271;179436270
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: Fn3-68
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1284
• 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	0.025	N	0.303	0.224	0.522875369128	gnomAD-4.0.0	7.96224E-06	None	None	None	None	N	None	0	2.28802E-05	None	0	0	None	0	0	8.57854E-06	0	3.02718E-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	0.6413	likely_pathogenic	0.6837	pathogenic	-1.761	Destabilizing	0.025	N	0.303	neutral	N	0.478593579	None	None	N
V/C	0.9506	likely_pathogenic	0.9506	pathogenic	-1.448	Destabilizing	0.997	D	0.77	deleterious	None	None	None	None	N
V/D	0.9941	likely_pathogenic	0.9937	pathogenic	-1.6	Destabilizing	0.983	D	0.832	deleterious	N	0.487115955	None	None	N
V/E	0.9756	likely_pathogenic	0.9744	pathogenic	-1.44	Destabilizing	0.975	D	0.745	deleterious	None	None	None	None	N
V/F	0.9097	likely_pathogenic	0.8935	pathogenic	-1.091	Destabilizing	0.983	D	0.771	deleterious	N	0.486991051	None	None	N
V/G	0.9243	likely_pathogenic	0.9234	pathogenic	-2.25	Highly Destabilizing	0.935	D	0.743	deleterious	N	0.460943396	None	None	N
V/H	0.994	likely_pathogenic	0.9933	pathogenic	-1.886	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
V/I	0.1372	likely_benign	0.1147	benign	-0.439	Destabilizing	0.773	D	0.535	neutral	N	0.491601632	None	None	N
V/K	0.9844	likely_pathogenic	0.9834	pathogenic	-1.331	Destabilizing	0.975	D	0.755	deleterious	None	None	None	None	N
V/L	0.7189	likely_pathogenic	0.6442	pathogenic	-0.439	Destabilizing	0.63	D	0.527	neutral	N	0.492716353	None	None	N
V/M	0.6477	likely_pathogenic	0.5944	pathogenic	-0.538	Destabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	N
V/N	0.9653	likely_pathogenic	0.964	pathogenic	-1.465	Destabilizing	0.987	D	0.845	deleterious	None	None	None	None	N
V/P	0.9835	likely_pathogenic	0.9837	pathogenic	-0.848	Destabilizing	0.987	D	0.788	deleterious	None	None	None	None	N
V/Q	0.9661	likely_pathogenic	0.966	pathogenic	-1.379	Destabilizing	0.987	D	0.806	deleterious	None	None	None	None	N
V/R	0.9742	likely_pathogenic	0.9738	pathogenic	-1.147	Destabilizing	0.987	D	0.845	deleterious	None	None	None	None	N
V/S	0.868	likely_pathogenic	0.8813	pathogenic	-2.184	Highly Destabilizing	0.95	D	0.718	prob.delet.	None	None	None	None	N
V/T	0.6608	likely_pathogenic	0.6738	pathogenic	-1.875	Destabilizing	0.916	D	0.553	neutral	None	None	None	None	N
V/W	0.9986	likely_pathogenic	0.9981	pathogenic	-1.45	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/Y	0.9912	likely_pathogenic	0.9898	pathogenic	-1.068	Destabilizing	0.996	D	0.781	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.