TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5388	16387;16388;16389	chr2:178733014;178733013;178733012	chr2:179597741;179597740;179597739
N2AB	5071	15436;15437;15438	chr2:178733014;178733013;178733012	chr2:179597741;179597740;179597739
N2A	4144	12655;12656;12657	chr2:178733014;178733013;178733012	chr2:179597741;179597740;179597739
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-37
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2785
• Predicted PPI site: I

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/L	rs796743868	-0.237	0.835	N	0.52	0.405	0.623711697247	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
V/L	rs796743868	-0.237	0.835	N	0.52	0.405	0.623711697247	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	0	4.79386E-04
V/L	rs796743868	-0.237	0.835	N	0.52	0.405	0.623711697247	gnomAD-4.0.0	6.57289E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	4.79386E-04

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	0.533	ambiguous	0.5684	pathogenic	-1.392	Destabilizing	0.91	D	0.689	prob.neutral	D	0.55458377	None	None	I
V/C	0.8987	likely_pathogenic	0.9121	pathogenic	-0.9	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
V/D	0.9586	likely_pathogenic	0.9547	pathogenic	-0.942	Destabilizing	0.996	D	0.852	deleterious	None	None	None	None	I
V/E	0.9173	likely_pathogenic	0.9113	pathogenic	-0.844	Destabilizing	0.994	D	0.821	deleterious	D	0.600632733	None	None	I
V/F	0.4002	ambiguous	0.3696	ambiguous	-0.823	Destabilizing	0.996	D	0.771	deleterious	None	None	None	None	I
V/G	0.7002	likely_pathogenic	0.7201	pathogenic	-1.807	Destabilizing	0.994	D	0.82	deleterious	D	0.600632733	None	None	I
V/H	0.9668	likely_pathogenic	0.9646	pathogenic	-1.344	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
V/I	0.0855	likely_benign	0.0806	benign	-0.313	Destabilizing	0.155	N	0.227	neutral	None	None	None	None	I
V/K	0.9578	likely_pathogenic	0.9533	pathogenic	-1.005	Destabilizing	0.996	D	0.828	deleterious	None	None	None	None	I
V/L	0.3997	ambiguous	0.3657	ambiguous	-0.313	Destabilizing	0.835	D	0.52	neutral	N	0.520634207	None	None	I
V/M	0.3718	ambiguous	0.3628	ambiguous	-0.337	Destabilizing	0.994	D	0.665	neutral	D	0.568190403	None	None	I
V/N	0.8971	likely_pathogenic	0.8938	pathogenic	-0.937	Destabilizing	0.996	D	0.86	deleterious	None	None	None	None	I
V/P	0.8947	likely_pathogenic	0.8881	pathogenic	-0.638	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	I
V/Q	0.9233	likely_pathogenic	0.9163	pathogenic	-0.923	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	I
V/R	0.934	likely_pathogenic	0.9273	pathogenic	-0.755	Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	I
V/S	0.7661	likely_pathogenic	0.7863	pathogenic	-1.584	Destabilizing	0.942	D	0.827	deleterious	None	None	None	None	I
V/T	0.588	likely_pathogenic	0.6083	pathogenic	-1.345	Destabilizing	0.304	N	0.396	neutral	None	None	None	None	I
V/W	0.9674	likely_pathogenic	0.9632	pathogenic	-1.102	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
V/Y	0.8753	likely_pathogenic	0.863	pathogenic	-0.743	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I

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.