TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26721	80386;80387;80388	chr2:178565971;178565970;178565969	chr2:179430698;179430697;179430696
N2AB	25080	75463;75464;75465	chr2:178565971;178565970;178565969	chr2:179430698;179430697;179430696
N2A	24153	72682;72683;72684	chr2:178565971;178565970;178565969	chr2:179430698;179430697;179430696
N2B	17656	53191;53192;53193	chr2:178565971;178565970;178565969	chr2:179430698;179430697;179430696
Novex-1	17781	53566;53567;53568	chr2:178565971;178565970;178565969	chr2:179430698;179430697;179430696
Novex-2	17848	53767;53768;53769	chr2:178565971;178565970;178565969	chr2:179430698;179430697;179430696
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: Fn3-82
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1383
• 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/E	None	None	0.067	N	0.366	0.092	0.0762999501168	gnomAD-4.0.0	6.84275E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87266E-05	0	0	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
D/A	0.7026	likely_pathogenic	0.7544	pathogenic	-1.415	Destabilizing	0.958	D	0.751	deleterious	N	0.473063851	None	None	N
D/C	0.9342	likely_pathogenic	0.9461	pathogenic	-0.727	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/E	0.4206	ambiguous	0.4601	ambiguous	-0.704	Destabilizing	0.067	N	0.366	neutral	N	0.330060892	None	None	N
D/F	0.9213	likely_pathogenic	0.9376	pathogenic	-1.237	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
D/G	0.8149	likely_pathogenic	0.8376	pathogenic	-1.805	Destabilizing	0.958	D	0.751	deleterious	N	0.474838278	None	None	N
D/H	0.8007	likely_pathogenic	0.8315	pathogenic	-1.258	Destabilizing	0.998	D	0.815	deleterious	N	0.509360673	None	None	N
D/I	0.9099	likely_pathogenic	0.9168	pathogenic	-0.328	Destabilizing	0.995	D	0.856	deleterious	None	None	None	None	N
D/K	0.9556	likely_pathogenic	0.9637	pathogenic	-1.465	Destabilizing	0.982	D	0.777	deleterious	None	None	None	None	N
D/L	0.877	likely_pathogenic	0.899	pathogenic	-0.328	Destabilizing	0.991	D	0.831	deleterious	None	None	None	None	N
D/M	0.9517	likely_pathogenic	0.9641	pathogenic	0.414	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
D/N	0.4792	ambiguous	0.5579	ambiguous	-1.6	Destabilizing	0.988	D	0.807	deleterious	N	0.498663677	None	None	N
D/P	0.9984	likely_pathogenic	0.9982	pathogenic	-0.671	Destabilizing	0.995	D	0.806	deleterious	None	None	None	None	N
D/Q	0.7752	likely_pathogenic	0.8268	pathogenic	-1.293	Destabilizing	0.982	D	0.827	deleterious	None	None	None	None	N
D/R	0.9495	likely_pathogenic	0.9566	pathogenic	-1.363	Destabilizing	0.991	D	0.808	deleterious	None	None	None	None	N
D/S	0.4916	ambiguous	0.5722	pathogenic	-2.273	Highly Destabilizing	0.968	D	0.721	prob.delet.	None	None	None	None	N
D/T	0.8314	likely_pathogenic	0.8575	pathogenic	-1.91	Destabilizing	0.991	D	0.796	deleterious	None	None	None	None	N
D/V	0.8122	likely_pathogenic	0.8305	pathogenic	-0.671	Destabilizing	0.994	D	0.82	deleterious	N	0.519961669	None	None	N
D/W	0.9827	likely_pathogenic	0.986	pathogenic	-1.336	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
D/Y	0.7285	likely_pathogenic	0.7618	pathogenic	-1.081	Destabilizing	0.999	D	0.85	deleterious	N	0.495970088	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.