TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30434	91525;91526;91527	chr2:178551231;178551230;178551229	chr2:179415958;179415957;179415956
N2AB	28793	86602;86603;86604	chr2:178551231;178551230;178551229	chr2:179415958;179415957;179415956
N2A	27866	83821;83822;83823	chr2:178551231;178551230;178551229	chr2:179415958;179415957;179415956
N2B	21369	64330;64331;64332	chr2:178551231;178551230;178551229	chr2:179415958;179415957;179415956
Novex-1	21494	64705;64706;64707	chr2:178551231;178551230;178551229	chr2:179415958;179415957;179415956
Novex-2	21561	64906;64907;64908	chr2:178551231;178551230;178551229	chr2:179415958;179415957;179415956
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: Fn3-110
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2921
• 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	0.822	N	0.437	0.281	0.574877809555	gnomAD-4.0.0	1.59268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85972E-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	0.5782	likely_pathogenic	0.6645	pathogenic	-1.775	Destabilizing	0.822	D	0.437	neutral	N	0.471461371	None	None	N
V/C	0.8516	likely_pathogenic	0.8833	pathogenic	-2.044	Highly Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
V/D	0.9567	likely_pathogenic	0.9681	pathogenic	-2.359	Highly Destabilizing	0.99	D	0.796	deleterious	N	0.517153309	None	None	N
V/E	0.8936	likely_pathogenic	0.9181	pathogenic	-2.269	Highly Destabilizing	0.993	D	0.746	deleterious	None	None	None	None	N
V/F	0.6337	likely_pathogenic	0.7109	pathogenic	-1.367	Destabilizing	0.942	D	0.733	prob.delet.	N	0.493074799	None	None	N
V/G	0.7594	likely_pathogenic	0.8225	pathogenic	-2.16	Highly Destabilizing	0.971	D	0.785	deleterious	N	0.506646377	None	None	N
V/H	0.9499	likely_pathogenic	0.964	pathogenic	-1.704	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
V/I	0.0831	likely_benign	0.082	benign	-0.763	Destabilizing	0.014	N	0.21	neutral	N	0.469668921	None	None	N
V/K	0.8631	likely_pathogenic	0.8877	pathogenic	-1.423	Destabilizing	0.978	D	0.745	deleterious	None	None	None	None	N
V/L	0.556	ambiguous	0.6129	pathogenic	-0.763	Destabilizing	0.247	N	0.315	neutral	N	0.469295324	None	None	N
V/M	0.3765	ambiguous	0.4479	ambiguous	-1.051	Destabilizing	0.956	D	0.634	neutral	None	None	None	None	N
V/N	0.8609	likely_pathogenic	0.8945	pathogenic	-1.566	Destabilizing	0.993	D	0.795	deleterious	None	None	None	None	N
V/P	0.9813	likely_pathogenic	0.9851	pathogenic	-1.07	Destabilizing	0.993	D	0.764	deleterious	None	None	None	None	N
V/Q	0.8597	likely_pathogenic	0.8857	pathogenic	-1.665	Destabilizing	0.993	D	0.759	deleterious	None	None	None	None	N
V/R	0.8231	likely_pathogenic	0.8493	pathogenic	-1.066	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
V/S	0.7237	likely_pathogenic	0.7911	pathogenic	-2.149	Highly Destabilizing	0.978	D	0.745	deleterious	None	None	None	None	N
V/T	0.461	ambiguous	0.5632	ambiguous	-1.932	Destabilizing	0.86	D	0.518	neutral	None	None	None	None	N
V/W	0.9799	likely_pathogenic	0.986	pathogenic	-1.624	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
V/Y	0.9125	likely_pathogenic	0.9353	pathogenic	-1.272	Destabilizing	0.978	D	0.749	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.