TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9224	27895;27896;27897	chr2:178712160;178712159;178712158	chr2:179576887;179576886;179576885
N2AB	8907	26944;26945;26946	chr2:178712160;178712159;178712158	chr2:179576887;179576886;179576885
N2A	7980	24163;24164;24165	chr2:178712160;178712159;178712158	chr2:179576887;179576886;179576885
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: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-78
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.2018
• 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
L/P	None	None	1.0	D	0.837	0.807	0.910524498493	gnomAD-4.0.0	1.59124E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41429E-04	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
L/A	0.9413	likely_pathogenic	0.9596	pathogenic	-2.367	Highly Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
L/C	0.9102	likely_pathogenic	0.9385	pathogenic	-1.607	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.9994	pathogenic	-3.049	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/E	0.9926	likely_pathogenic	0.9952	pathogenic	-2.72	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/F	0.1426	likely_benign	0.1499	benign	-1.343	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
L/G	0.9896	likely_pathogenic	0.9934	pathogenic	-2.984	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/H	0.9512	likely_pathogenic	0.9675	pathogenic	-2.744	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/I	0.1364	likely_benign	0.1612	benign	-0.514	Destabilizing	0.999	D	0.657	neutral	D	0.553071135	None	None	N
L/K	0.9844	likely_pathogenic	0.9889	pathogenic	-1.68	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/M	0.2235	likely_benign	0.2517	benign	-0.741	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
L/N	0.9933	likely_pathogenic	0.9953	pathogenic	-2.38	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
L/P	0.9957	likely_pathogenic	0.9976	pathogenic	-1.122	Destabilizing	1.0	D	0.837	deleterious	D	0.62357775	None	None	N
L/Q	0.952	likely_pathogenic	0.9681	pathogenic	-2.003	Highly Destabilizing	1.0	D	0.836	deleterious	D	0.639597111	None	None	N
L/R	0.9646	likely_pathogenic	0.9767	pathogenic	-1.904	Destabilizing	1.0	D	0.828	deleterious	D	0.639597111	None	None	N
L/S	0.9821	likely_pathogenic	0.9886	pathogenic	-2.95	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/T	0.9592	likely_pathogenic	0.9709	pathogenic	-2.446	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/V	0.2234	likely_benign	0.2845	benign	-1.122	Destabilizing	0.999	D	0.666	neutral	D	0.590297842	None	None	N
L/W	0.7334	likely_pathogenic	0.8139	pathogenic	-1.726	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
L/Y	0.8191	likely_pathogenic	0.8475	pathogenic	-1.467	Destabilizing	1.0	D	0.798	deleterious	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.