TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7963	24112;24113;24114	chr2:178719605;178719604;178719603	chr2:179584332;179584331;179584330
N2AB	7646	23161;23162;23163	chr2:178719605;178719604;178719603	chr2:179584332;179584331;179584330
N2A	6719	20380;20381;20382	chr2:178719605;178719604;178719603	chr2:179584332;179584331;179584330
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-64
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0935
• 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	rs1444280524	-1.255	0.998	D	0.763	0.523	0.683767819358	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/M	rs1444280524	-1.255	0.998	D	0.763	0.523	0.683767819358	gnomAD-4.0.0	1.36895E-06	None	None	None	None	N	None	0	0	None	0	2.51953E-05	None	0	0	0	1.16004E-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	0.7113	likely_pathogenic	0.6774	pathogenic	-2.339	Highly Destabilizing	0.543	D	0.351	neutral	N	0.427979802	None	None	N
V/C	0.9733	likely_pathogenic	0.9724	pathogenic	-2.098	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/D	0.9938	likely_pathogenic	0.9943	pathogenic	-3.19	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
V/E	0.98	likely_pathogenic	0.9802	pathogenic	-2.928	Highly Destabilizing	0.998	D	0.867	deleterious	D	0.559437519	None	None	N
V/F	0.8615	likely_pathogenic	0.8406	pathogenic	-1.255	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
V/G	0.8179	likely_pathogenic	0.8223	pathogenic	-2.903	Highly Destabilizing	0.997	D	0.845	deleterious	N	0.514581729	None	None	N
V/H	0.9979	likely_pathogenic	0.9979	pathogenic	-2.608	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/I	0.1128	likely_benign	0.111	benign	-0.729	Destabilizing	0.611	D	0.279	neutral	None	None	None	None	N
V/K	0.9917	likely_pathogenic	0.9922	pathogenic	-1.848	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
V/L	0.6597	likely_pathogenic	0.6222	pathogenic	-0.729	Destabilizing	0.948	D	0.621	neutral	N	0.512162192	None	None	N
V/M	0.6719	likely_pathogenic	0.6353	pathogenic	-1.088	Destabilizing	0.998	D	0.763	deleterious	D	0.54766314	None	None	N
V/N	0.9849	likely_pathogenic	0.9856	pathogenic	-2.348	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/P	0.9971	likely_pathogenic	0.9964	pathogenic	-1.243	Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
V/Q	0.9872	likely_pathogenic	0.9866	pathogenic	-2.112	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/R	0.9861	likely_pathogenic	0.986	pathogenic	-1.771	Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
V/S	0.9434	likely_pathogenic	0.9376	pathogenic	-2.936	Highly Destabilizing	0.995	D	0.841	deleterious	None	None	None	None	N
V/T	0.8628	likely_pathogenic	0.8518	pathogenic	-2.526	Highly Destabilizing	0.992	D	0.704	prob.neutral	None	None	None	None	N
V/W	0.9974	likely_pathogenic	0.9972	pathogenic	-1.783	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9852	likely_pathogenic	0.984	pathogenic	-1.469	Destabilizing	1.0	D	0.827	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.