TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28536	85831;85832;85833	chr2:178560526;178560525;178560524	chr2:179425253;179425252;179425251
N2AB	26895	80908;80909;80910	chr2:178560526;178560525;178560524	chr2:179425253;179425252;179425251
N2A	25968	78127;78128;78129	chr2:178560526;178560525;178560524	chr2:179425253;179425252;179425251
N2B	19471	58636;58637;58638	chr2:178560526;178560525;178560524	chr2:179425253;179425252;179425251
Novex-1	19596	59011;59012;59013	chr2:178560526;178560525;178560524	chr2:179425253;179425252;179425251
Novex-2	19663	59212;59213;59214	chr2:178560526;178560525;178560524	chr2:179425253;179425252;179425251
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-95
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.306
• 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
P/T	rs1703229481	None	0.124	N	0.481	0.141	0.134241683229	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
P/T	rs1703229481	None	0.124	N	0.481	0.141	0.134241683229	gnomAD-4.0.0	3.84685E-06	None	None	None	None	I	None	3.38662E-05	0	None	0	0	None	0	0	2.39412E-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
P/A	0.0713	likely_benign	0.0717	benign	-1.506	Destabilizing	None	N	0.311	neutral	N	0.505645577	None	None	I
P/C	0.3661	ambiguous	0.3896	ambiguous	-0.899	Destabilizing	0.909	D	0.739	prob.delet.	None	None	None	None	I
P/D	0.6265	likely_pathogenic	0.5656	pathogenic	-1.502	Destabilizing	0.396	N	0.515	neutral	None	None	None	None	I
P/E	0.4366	ambiguous	0.4206	ambiguous	-1.531	Destabilizing	0.157	N	0.482	neutral	None	None	None	None	I
P/F	0.4319	ambiguous	0.4334	ambiguous	-1.197	Destabilizing	0.567	D	0.738	prob.delet.	None	None	None	None	I
P/G	0.2807	likely_benign	0.2697	benign	-1.789	Destabilizing	0.157	N	0.57	neutral	None	None	None	None	I
P/H	0.2558	likely_benign	0.2558	benign	-1.313	Destabilizing	0.005	N	0.538	neutral	D	0.528137085	None	None	I
P/I	0.35	ambiguous	0.3471	ambiguous	-0.835	Destabilizing	0.567	D	0.695	prob.neutral	None	None	None	None	I
P/K	0.4458	ambiguous	0.4339	ambiguous	-1.332	Destabilizing	0.157	N	0.496	neutral	None	None	None	None	I
P/L	0.2179	likely_benign	0.2065	benign	-0.835	Destabilizing	0.124	N	0.64	neutral	D	0.52560219	None	None	I
P/M	0.3543	ambiguous	0.3622	ambiguous	-0.596	Destabilizing	0.909	D	0.675	neutral	None	None	None	None	I
P/N	0.4002	ambiguous	0.3994	ambiguous	-1.035	Destabilizing	0.396	N	0.605	neutral	None	None	None	None	I
P/Q	0.2793	likely_benign	0.267	benign	-1.268	Destabilizing	0.567	D	0.562	neutral	None	None	None	None	I
P/R	0.3493	ambiguous	0.318	benign	-0.715	Destabilizing	0.497	N	0.633	neutral	D	0.527123127	None	None	I
P/S	0.1135	likely_benign	0.1117	benign	-1.475	Destabilizing	0.001	N	0.414	neutral	N	0.508676477	None	None	I
P/T	0.134	likely_benign	0.1347	benign	-1.411	Destabilizing	0.124	N	0.481	neutral	N	0.509436946	None	None	I
P/V	0.2266	likely_benign	0.2326	benign	-1.025	Destabilizing	0.157	N	0.581	neutral	None	None	None	None	I
P/W	0.6017	likely_pathogenic	0.5699	pathogenic	-1.349	Destabilizing	0.968	D	0.761	deleterious	None	None	None	None	I
P/Y	0.3696	ambiguous	0.3776	ambiguous	-1.106	Destabilizing	0.396	N	0.727	prob.delet.	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.