TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35662	107209;107210;107211	chr2:178528767;178528766;178528765	chr2:179393494;179393493;179393492
N2AB	34021	102286;102287;102288	chr2:178528767;178528766;178528765	chr2:179393494;179393493;179393492
N2A	33094	99505;99506;99507	chr2:178528767;178528766;178528765	chr2:179393494;179393493;179393492
N2B	26597	80014;80015;80016	chr2:178528767;178528766;178528765	chr2:179393494;179393493;179393492
Novex-1	26722	80389;80390;80391	chr2:178528767;178528766;178528765	chr2:179393494;179393493;179393492
Novex-2	26789	80590;80591;80592	chr2:178528767;178528766;178528765	chr2:179393494;179393493;179393492
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-167
• Domain position: 56
• Structural Position: 138
• Q(SASA): 0.0532
• 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
L/P	None	None	1.0	N	0.902	0.742	0.88178623801	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.9447	likely_pathogenic	0.9505	pathogenic	-2.392	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
L/C	0.9557	likely_pathogenic	0.9655	pathogenic	-1.591	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9997	pathogenic	-3.046	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/E	0.9964	likely_pathogenic	0.9971	pathogenic	-2.706	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/F	0.6999	likely_pathogenic	0.7012	pathogenic	-1.47	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
L/G	0.9927	likely_pathogenic	0.9938	pathogenic	-3.023	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/H	0.9907	likely_pathogenic	0.9925	pathogenic	-2.925	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/I	0.3177	likely_benign	0.3187	benign	-0.497	Destabilizing	0.999	D	0.64	neutral	N	0.489949059	None	None	N
L/K	0.9909	likely_pathogenic	0.9924	pathogenic	-1.742	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/M	0.4159	ambiguous	0.4103	ambiguous	-0.689	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/N	0.9972	likely_pathogenic	0.9976	pathogenic	-2.495	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/P	0.9977	likely_pathogenic	0.9985	pathogenic	-1.119	Destabilizing	1.0	D	0.902	deleterious	N	0.492029359	None	None	N
L/Q	0.9822	likely_pathogenic	0.9847	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.905	deleterious	N	0.492029359	None	None	N
L/R	0.9818	likely_pathogenic	0.9841	pathogenic	-2.01	Highly Destabilizing	1.0	D	0.898	deleterious	N	0.492029359	None	None	N
L/S	0.9948	likely_pathogenic	0.9957	pathogenic	-3.044	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/T	0.9842	likely_pathogenic	0.9855	pathogenic	-2.523	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/V	0.3889	ambiguous	0.3779	ambiguous	-1.119	Destabilizing	0.999	D	0.651	neutral	N	0.490815851	None	None	N
L/W	0.9749	likely_pathogenic	0.9787	pathogenic	-1.883	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/Y	0.9769	likely_pathogenic	0.9793	pathogenic	-1.615	Destabilizing	1.0	D	0.853	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.