TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14582	43969;43970;43971	chr2:178632150;178632149;178632148	chr2:179496877;179496876;179496875
N2AB	12941	39046;39047;39048	chr2:178632150;178632149;178632148	chr2:179496877;179496876;179496875
N2A	12014	36265;36266;36267	chr2:178632150;178632149;178632148	chr2:179496877;179496876;179496875
N2B	5517	16774;16775;16776	chr2:178632150;178632149;178632148	chr2:179496877;179496876;179496875
Novex-1	5642	17149;17150;17151	chr2:178632150;178632149;178632148	chr2:179496877;179496876;179496875
Novex-2	5709	17350;17351;17352	chr2:178632150;178632149;178632148	chr2:179496877;179496876;179496875
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-96
• Domain position: 86
• Structural Position: 178
• Q(SASA): 0.771
• Predicted PPI site: I

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/R	rs2059886153	None	0.996	N	0.67	0.506	0.816327850401	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/R	rs2059886153	None	0.996	N	0.67	0.506	0.816327850401	gnomAD-4.0.0	6.57367E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47072E-05	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	0.26	likely_benign	0.2286	benign	-0.863	Destabilizing	0.944	D	0.579	neutral	None	None	None	None	I
L/C	0.6127	likely_pathogenic	0.636	pathogenic	-0.606	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	I
L/D	0.6865	likely_pathogenic	0.6626	pathogenic	-0.436	Destabilizing	0.997	D	0.703	prob.neutral	None	None	None	None	I
L/E	0.2809	likely_benign	0.2471	benign	-0.516	Destabilizing	0.997	D	0.688	prob.neutral	None	None	None	None	I
L/F	0.1764	likely_benign	0.1666	benign	-0.757	Destabilizing	0.978	D	0.662	neutral	D	0.542699484	None	None	I
L/G	0.6167	likely_pathogenic	0.6062	pathogenic	-1.065	Destabilizing	0.992	D	0.673	neutral	None	None	None	None	I
L/H	0.2644	likely_benign	0.2572	benign	-0.311	Destabilizing	0.999	D	0.731	prob.delet.	D	0.541657077	None	None	I
L/I	0.0841	likely_benign	0.0658	benign	-0.439	Destabilizing	0.085	N	0.301	neutral	N	0.478048025	None	None	I
L/K	0.2319	likely_benign	0.2146	benign	-0.553	Destabilizing	0.992	D	0.627	neutral	None	None	None	None	I
L/M	0.1275	likely_benign	0.117	benign	-0.41	Destabilizing	0.983	D	0.667	neutral	None	None	None	None	I
L/N	0.439	ambiguous	0.4047	ambiguous	-0.291	Destabilizing	0.997	D	0.706	prob.neutral	None	None	None	None	I
L/P	0.6919	likely_pathogenic	0.7793	pathogenic	-0.547	Destabilizing	0.996	D	0.705	prob.neutral	D	0.542699484	None	None	I
L/Q	0.1454	likely_benign	0.1422	benign	-0.535	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
L/R	0.1817	likely_benign	0.1761	benign	0.059	Stabilizing	0.996	D	0.67	neutral	N	0.486591784	None	None	I
L/S	0.256	likely_benign	0.2348	benign	-0.759	Destabilizing	0.992	D	0.619	neutral	None	None	None	None	I
L/T	0.1803	likely_benign	0.1536	benign	-0.731	Destabilizing	0.983	D	0.611	neutral	None	None	None	None	I
L/V	0.1017	likely_benign	0.084	benign	-0.547	Destabilizing	0.476	N	0.517	neutral	N	0.497969762	None	None	I
L/W	0.2762	likely_benign	0.3026	benign	-0.77	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
L/Y	0.4583	ambiguous	0.4581	ambiguous	-0.539	Destabilizing	0.992	D	0.683	prob.neutral	None	None	None	None	I

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.