TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6069	18430;18431;18432	chr2:178730195;178730194;178730193	chr2:179594922;179594921;179594920
N2AB	5752	17479;17480;17481	chr2:178730195;178730194;178730193	chr2:179594922;179594921;179594920
N2A	4825	14698;14699;14700	chr2:178730195;178730194;178730193	chr2:179594922;179594921;179594920
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-44
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0743
• 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/I	None	None	0.79	N	0.377	0.37	0.308904156042	gnomAD-4.0.0	1.59197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	0
L/P	None	None	1.0	D	0.915	0.754	0.898168116285	gnomAD-4.0.0	1.59197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85894E-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
L/A	0.8715	likely_pathogenic	0.8896	pathogenic	-2.732	Highly Destabilizing	0.994	D	0.741	deleterious	None	None	None	None	N
L/C	0.8926	likely_pathogenic	0.9045	pathogenic	-2.196	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/D	0.9983	likely_pathogenic	0.9987	pathogenic	-3.415	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/E	0.9867	likely_pathogenic	0.9892	pathogenic	-3.078	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/F	0.4015	ambiguous	0.5028	ambiguous	-1.631	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
L/G	0.9777	likely_pathogenic	0.9824	pathogenic	-3.376	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/H	0.9716	likely_pathogenic	0.9769	pathogenic	-3.109	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/I	0.1628	likely_benign	0.1683	benign	-0.794	Destabilizing	0.79	D	0.377	neutral	N	0.511961609	None	None	N
L/K	0.9826	likely_pathogenic	0.9861	pathogenic	-2.129	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/M	0.2646	likely_benign	0.2959	benign	-1.074	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
L/N	0.9927	likely_pathogenic	0.9936	pathogenic	-2.851	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/P	0.9884	likely_pathogenic	0.9897	pathogenic	-1.43	Destabilizing	1.0	D	0.915	deleterious	D	0.568493328	None	None	N
L/Q	0.9506	likely_pathogenic	0.9612	pathogenic	-2.474	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.568493328	None	None	N
L/R	0.9614	likely_pathogenic	0.9674	pathogenic	-2.225	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.557137023	None	None	N
L/S	0.9772	likely_pathogenic	0.9826	pathogenic	-3.474	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/T	0.9213	likely_pathogenic	0.9317	pathogenic	-2.955	Highly Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
L/V	0.1994	likely_benign	0.2114	benign	-1.43	Destabilizing	0.962	D	0.692	prob.neutral	D	0.532485401	None	None	N
L/W	0.846	likely_pathogenic	0.8787	pathogenic	-2.041	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/Y	0.9161	likely_pathogenic	0.9354	pathogenic	-1.809	Destabilizing	1.0	D	0.825	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.