TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9206	27841;27842;27843	chr2:178712214;178712213;178712212	chr2:179576941;179576940;179576939
N2AB	8889	26890;26891;26892	chr2:178712214;178712213;178712212	chr2:179576941;179576940;179576939
N2A	7962	24109;24110;24111	chr2:178712214;178712213;178712212	chr2:179576941;179576940;179576939
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-78
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4276
• 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
Y/C	None	None	1.0	N	0.603	0.505	0.521970134296	gnomAD-4.0.0	1.36922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99967E-07	0	1.65755E-05

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
Y/A	0.5402	ambiguous	0.5117	ambiguous	-1.326	Destabilizing	0.942	D	0.527	neutral	None	None	None	None	N
Y/C	0.1894	likely_benign	0.171	benign	-0.55	Destabilizing	1.0	D	0.603	neutral	N	0.496897731	None	None	N
Y/D	0.5182	ambiguous	0.4762	ambiguous	0.253	Stabilizing	0.989	D	0.563	neutral	N	0.481805216	None	None	N
Y/E	0.7204	likely_pathogenic	0.6882	pathogenic	0.305	Stabilizing	0.991	D	0.499	neutral	None	None	None	None	N
Y/F	0.0998	likely_benign	0.0956	benign	-0.42	Destabilizing	0.071	N	0.265	neutral	N	0.496117309	None	None	N
Y/G	0.5974	likely_pathogenic	0.5531	ambiguous	-1.578	Destabilizing	0.97	D	0.506	neutral	None	None	None	None	N
Y/H	0.1994	likely_benign	0.1838	benign	-0.073	Destabilizing	0.998	D	0.505	neutral	D	0.529979167	None	None	N
Y/I	0.4701	ambiguous	0.4485	ambiguous	-0.61	Destabilizing	0.991	D	0.499	neutral	None	None	None	None	N
Y/K	0.6451	likely_pathogenic	0.6239	pathogenic	-0.57	Destabilizing	0.991	D	0.507	neutral	None	None	None	None	N
Y/L	0.5425	ambiguous	0.5157	ambiguous	-0.61	Destabilizing	0.942	D	0.483	neutral	None	None	None	None	N
Y/M	0.7048	likely_pathogenic	0.6723	pathogenic	-0.577	Destabilizing	1.0	D	0.532	neutral	None	None	None	None	N
Y/N	0.3092	likely_benign	0.2699	benign	-1.0	Destabilizing	0.989	D	0.55	neutral	D	0.522090402	None	None	N
Y/P	0.9805	likely_pathogenic	0.9814	pathogenic	-0.837	Destabilizing	0.996	D	0.619	neutral	None	None	None	None	N
Y/Q	0.5259	ambiguous	0.4955	ambiguous	-0.851	Destabilizing	0.996	D	0.538	neutral	None	None	None	None	N
Y/R	0.3842	ambiguous	0.3727	ambiguous	-0.277	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	N
Y/S	0.2285	likely_benign	0.2007	benign	-1.463	Destabilizing	0.489	N	0.346	neutral	N	0.486745677	None	None	N
Y/T	0.4282	ambiguous	0.3812	ambiguous	-1.317	Destabilizing	0.942	D	0.489	neutral	None	None	None	None	N
Y/V	0.3391	likely_benign	0.3332	benign	-0.837	Destabilizing	0.97	D	0.487	neutral	None	None	None	None	N
Y/W	0.5215	ambiguous	0.5167	ambiguous	-0.26	Destabilizing	1.0	D	0.505	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.