TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9717	29374;29375;29376	chr2:178706725;178706724;178706723	chr2:179571452;179571451;179571450
N2AB	9400	28423;28424;28425	chr2:178706725;178706724;178706723	chr2:179571452;179571451;179571450
N2A	8473	25642;25643;25644	chr2:178706725;178706724;178706723	chr2:179571452;179571451;179571450
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-83
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.122
• 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
F/S	None	None	1.0	None	0.881	0.764	0.904332106958	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
F/A	0.9985	likely_pathogenic	0.9951	pathogenic	-2.292	Highly Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
F/C	0.9924	likely_pathogenic	0.9703	pathogenic	-1.305	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
F/D	0.9999	likely_pathogenic	0.9998	pathogenic	-3.32	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
F/E	0.9999	likely_pathogenic	0.9997	pathogenic	-3.081	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
F/G	0.9995	likely_pathogenic	0.9981	pathogenic	-2.728	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
F/H	0.9985	likely_pathogenic	0.9962	pathogenic	-2.194	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
F/I	0.9429	likely_pathogenic	0.8706	pathogenic	-0.845	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
F/K	0.9999	likely_pathogenic	0.9997	pathogenic	-2.114	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
F/L	0.9945	likely_pathogenic	0.9758	pathogenic	-0.845	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
F/M	0.9799	likely_pathogenic	0.9432	pathogenic	-0.694	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
F/N	0.9996	likely_pathogenic	0.9989	pathogenic	-2.858	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
F/P	1.0	likely_pathogenic	0.9999	pathogenic	-1.343	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
F/Q	0.9997	likely_pathogenic	0.9993	pathogenic	-2.555	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
F/R	0.9995	likely_pathogenic	0.9987	pathogenic	-2.223	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
F/S	0.9994	likely_pathogenic	0.9973	pathogenic	-3.155	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
F/T	0.9993	likely_pathogenic	0.9978	pathogenic	-2.788	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
F/V	0.9569	likely_pathogenic	0.8852	pathogenic	-1.343	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
F/W	0.9822	likely_pathogenic	0.9615	pathogenic	-0.457	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
F/Y	0.9031	likely_pathogenic	0.7656	pathogenic	-0.859	Destabilizing	0.999	D	0.618	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.