TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4917	14974;14975;14976	chr2:178735697;178735696;178735695	chr2:179600424;179600423;179600422
N2AB	4600	14023;14024;14025	chr2:178735697;178735696;178735695	chr2:179600424;179600423;179600422
N2A	3673	11242;11243;11244	chr2:178735697;178735696;178735695	chr2:179600424;179600423;179600422
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-32
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.2959
• 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/I	None	None	0.997	D	0.583	0.416	0.70802241665	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	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	0.4317	ambiguous	0.4679	ambiguous	-1.716	Destabilizing	0.999	D	0.566	neutral	D	0.644855894	None	None	N
V/C	0.9074	likely_pathogenic	0.9149	pathogenic	-1.333	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/D	0.8625	likely_pathogenic	0.8948	pathogenic	-1.325	Destabilizing	1.0	D	0.808	deleterious	D	0.797806706	None	None	N
V/E	0.8131	likely_pathogenic	0.8464	pathogenic	-1.263	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/F	0.4781	ambiguous	0.5567	ambiguous	-1.283	Destabilizing	1.0	D	0.816	deleterious	D	0.687520674	None	None	N
V/G	0.4941	ambiguous	0.5325	ambiguous	-2.111	Highly Destabilizing	1.0	D	0.81	deleterious	D	0.797806706	None	None	N
V/H	0.9518	likely_pathogenic	0.9644	pathogenic	-1.676	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
V/I	0.1102	likely_benign	0.1253	benign	-0.704	Destabilizing	0.997	D	0.583	neutral	D	0.663056301	None	None	N
V/K	0.8973	likely_pathogenic	0.9213	pathogenic	-1.352	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/L	0.4583	ambiguous	0.5283	ambiguous	-0.704	Destabilizing	0.997	D	0.588	neutral	D	0.66581112	None	None	N
V/M	0.3359	likely_benign	0.3887	ambiguous	-0.603	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/N	0.7628	likely_pathogenic	0.8125	pathogenic	-1.251	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/P	0.7751	likely_pathogenic	0.7994	pathogenic	-1.007	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
V/Q	0.8725	likely_pathogenic	0.8998	pathogenic	-1.315	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/R	0.8765	likely_pathogenic	0.9021	pathogenic	-0.96	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
V/S	0.6579	likely_pathogenic	0.7026	pathogenic	-1.906	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/T	0.5398	ambiguous	0.5914	pathogenic	-1.709	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
V/W	0.9662	likely_pathogenic	0.9751	pathogenic	-1.513	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
V/Y	0.8768	likely_pathogenic	0.9009	pathogenic	-1.196	Destabilizing	1.0	D	0.808	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.