TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5044	15355;15356;15357	chr2:178734794;178734793;178734792	chr2:179599521;179599520;179599519
N2AB	4727	14404;14405;14406	chr2:178734794;178734793;178734792	chr2:179599521;179599520;179599519
N2A	3800	11623;11624;11625	chr2:178734794;178734793;178734792	chr2:179599521;179599520;179599519
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-33
• Domain position: 64
• Structural Position: 144
• Q(SASA): 0.0916
• 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/L	None	None	0.002	N	0.146	0.236	0.418964662724	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.3475	ambiguous	0.3214	benign	-1.775	Destabilizing	0.201	N	0.437	neutral	N	0.424407137	None	None	N
V/C	0.8395	likely_pathogenic	0.844	pathogenic	-1.623	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	N
V/D	0.9581	likely_pathogenic	0.952	pathogenic	-2.473	Highly Destabilizing	0.85	D	0.646	neutral	None	None	None	None	N
V/E	0.922	likely_pathogenic	0.9144	pathogenic	-2.433	Highly Destabilizing	0.549	D	0.613	neutral	D	0.596121865	None	None	N
V/F	0.5348	ambiguous	0.5122	ambiguous	-1.412	Destabilizing	0.739	D	0.633	neutral	None	None	None	None	N
V/G	0.5715	likely_pathogenic	0.5262	ambiguous	-2.129	Highly Destabilizing	0.549	D	0.605	neutral	D	0.596121865	None	None	N
V/H	0.9758	likely_pathogenic	0.9727	pathogenic	-1.672	Destabilizing	0.992	D	0.609	neutral	None	None	None	None	N
V/I	0.1006	likely_benign	0.0941	benign	-0.866	Destabilizing	0.201	N	0.453	neutral	N	0.476129844	None	None	N
V/K	0.9499	likely_pathogenic	0.941	pathogenic	-1.487	Destabilizing	0.617	D	0.574	neutral	None	None	None	None	N
V/L	0.3071	likely_benign	0.2667	benign	-0.866	Destabilizing	0.002	N	0.146	neutral	N	0.465218391	None	None	N
V/M	0.1978	likely_benign	0.1835	benign	-0.814	Destabilizing	0.059	N	0.349	neutral	None	None	None	None	N
V/N	0.8611	likely_pathogenic	0.8489	pathogenic	-1.508	Destabilizing	0.85	D	0.648	neutral	None	None	None	None	N
V/P	0.9368	likely_pathogenic	0.8906	pathogenic	-1.138	Destabilizing	0.92	D	0.629	neutral	None	None	None	None	N
V/Q	0.9097	likely_pathogenic	0.9021	pathogenic	-1.678	Destabilizing	0.92	D	0.625	neutral	None	None	None	None	N
V/R	0.9255	likely_pathogenic	0.9175	pathogenic	-0.996	Destabilizing	0.92	D	0.65	neutral	None	None	None	None	N
V/S	0.6009	likely_pathogenic	0.576	pathogenic	-2.001	Highly Destabilizing	0.059	N	0.451	neutral	None	None	None	None	N
V/T	0.4213	ambiguous	0.4051	ambiguous	-1.85	Destabilizing	0.447	N	0.487	neutral	None	None	None	None	N
V/W	0.9805	likely_pathogenic	0.9793	pathogenic	-1.685	Destabilizing	0.992	D	0.605	neutral	None	None	None	None	N
V/Y	0.9437	likely_pathogenic	0.9417	pathogenic	-1.37	Destabilizing	0.92	D	0.636	neutral	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.