TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26177	78754;78755;78756	chr2:178567603;178567602;178567601	chr2:179432330;179432329;179432328
N2AB	24536	73831;73832;73833	chr2:178567603;178567602;178567601	chr2:179432330;179432329;179432328
N2A	23609	71050;71051;71052	chr2:178567603;178567602;178567601	chr2:179432330;179432329;179432328
N2B	17112	51559;51560;51561	chr2:178567603;178567602;178567601	chr2:179432330;179432329;179432328
Novex-1	17237	51934;51935;51936	chr2:178567603;178567602;178567601	chr2:179432330;179432329;179432328
Novex-2	17304	52135;52136;52137	chr2:178567603;178567602;178567601	chr2:179432330;179432329;179432328
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-78
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.9028
• 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
D/N	None	None	0.682	N	0.675	0.153	0.177238962908	gnomAD-4.0.0	1.59637E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43686E-05	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
D/A	0.1057	likely_benign	0.0967	benign	-0.288	Destabilizing	0.518	D	0.695	prob.delet.	N	0.438737434	None	None	N
D/C	0.4862	ambiguous	0.4229	ambiguous	0.254	Stabilizing	0.996	D	0.839	deleterious	None	None	None	None	N
D/E	0.0883	likely_benign	0.082	benign	-0.231	Destabilizing	0.003	N	0.178	neutral	N	0.343304256	None	None	N
D/F	0.4106	ambiguous	0.3376	benign	-0.429	Destabilizing	0.909	D	0.821	deleterious	None	None	None	None	N
D/G	0.1601	likely_benign	0.1466	benign	-0.426	Destabilizing	0.813	D	0.643	neutral	N	0.49482279	None	None	N
D/H	0.2204	likely_benign	0.195	benign	-0.289	Destabilizing	0.983	D	0.716	prob.delet.	N	0.509426883	None	None	N
D/I	0.1982	likely_benign	0.179	benign	0.017	Stabilizing	0.833	D	0.697	prob.delet.	None	None	None	None	N
D/K	0.2303	likely_benign	0.2019	benign	0.567	Stabilizing	0.587	D	0.702	prob.delet.	None	None	None	None	N
D/L	0.2293	likely_benign	0.204	benign	0.017	Stabilizing	0.587	D	0.725	deleterious	None	None	None	None	N
D/M	0.4276	ambiguous	0.3755	ambiguous	0.257	Stabilizing	0.987	D	0.799	deleterious	None	None	None	None	N
D/N	0.0877	likely_benign	0.0836	benign	0.332	Stabilizing	0.682	D	0.675	prob.neutral	N	0.447626276	None	None	N
D/P	0.432	ambiguous	0.383	ambiguous	-0.065	Destabilizing	0.953	D	0.716	prob.delet.	None	None	None	None	N
D/Q	0.218	likely_benign	0.1928	benign	0.326	Stabilizing	0.833	D	0.623	neutral	None	None	None	None	N
D/R	0.2947	likely_benign	0.257	benign	0.555	Stabilizing	0.909	D	0.802	deleterious	None	None	None	None	N
D/S	0.109	likely_benign	0.1005	benign	0.26	Stabilizing	0.74	D	0.545	neutral	None	None	None	None	N
D/T	0.1768	likely_benign	0.1615	benign	0.372	Stabilizing	0.74	D	0.727	deleterious	None	None	None	None	N
D/V	0.119	likely_benign	0.1085	benign	-0.065	Destabilizing	0.007	N	0.538	neutral	N	0.482856357	None	None	N
D/W	0.833	likely_pathogenic	0.7861	pathogenic	-0.343	Destabilizing	0.996	D	0.841	deleterious	None	None	None	None	N
D/Y	0.1576	likely_benign	0.1389	benign	-0.198	Destabilizing	0.938	D	0.819	deleterious	N	0.483029716	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.