TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5111	15556;15557;15558	chr2:178734493;178734492;178734491	chr2:179599220;179599219;179599218
N2AB	4794	14605;14606;14607	chr2:178734493;178734492;178734491	chr2:179599220;179599219;179599218
N2A	3867	11824;11825;11826	chr2:178734493;178734492;178734491	chr2:179599220;179599219;179599218
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-34
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.639
• 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	0.026	D	0.22	0.273	0.158396225186	gnomAD-4.0.0	6.84257E-07	None	None	None	None	N	None	2.98757E-05	0	None	0	0	None	0	0	0	0	0
D/G	None	None	0.896	D	0.488	0.669	0.412587454835	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.5602	ambiguous	0.6388	pathogenic	-0.633	Destabilizing	0.896	D	0.557	neutral	D	0.696473539	None	None	N
D/C	0.8957	likely_pathogenic	0.9259	pathogenic	-0.36	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
D/E	0.3171	likely_benign	0.391	ambiguous	-0.495	Destabilizing	0.026	N	0.22	neutral	D	0.569902997	None	None	N
D/F	0.9076	likely_pathogenic	0.9437	pathogenic	-0.2	Destabilizing	0.996	D	0.613	neutral	None	None	None	None	N
D/G	0.2203	likely_benign	0.2591	benign	-0.933	Destabilizing	0.896	D	0.488	neutral	D	0.555650191	None	None	N
D/H	0.7782	likely_pathogenic	0.8186	pathogenic	-0.308	Destabilizing	0.984	D	0.468	neutral	D	0.707260753	None	None	N
D/I	0.9023	likely_pathogenic	0.9409	pathogenic	0.148	Stabilizing	0.996	D	0.617	neutral	None	None	None	None	N
D/K	0.8798	likely_pathogenic	0.9047	pathogenic	-0.409	Destabilizing	0.851	D	0.491	neutral	None	None	None	None	N
D/L	0.8197	likely_pathogenic	0.8857	pathogenic	0.148	Stabilizing	0.988	D	0.593	neutral	None	None	None	None	N
D/M	0.9288	likely_pathogenic	0.9555	pathogenic	0.402	Stabilizing	0.999	D	0.617	neutral	None	None	None	None	N
D/N	0.1722	likely_benign	0.1748	benign	-0.776	Destabilizing	0.046	N	0.191	neutral	N	0.497169306	None	None	N
D/P	0.9915	likely_pathogenic	0.995	pathogenic	-0.089	Destabilizing	0.988	D	0.463	neutral	None	None	None	None	N
D/Q	0.7684	likely_pathogenic	0.8233	pathogenic	-0.663	Destabilizing	0.952	D	0.378	neutral	None	None	None	None	N
D/R	0.8823	likely_pathogenic	0.9054	pathogenic	-0.118	Destabilizing	0.976	D	0.536	neutral	None	None	None	None	N
D/S	0.3835	ambiguous	0.4316	ambiguous	-0.978	Destabilizing	0.919	D	0.459	neutral	None	None	None	None	N
D/T	0.7932	likely_pathogenic	0.863	pathogenic	-0.74	Destabilizing	0.919	D	0.503	neutral	None	None	None	None	N
D/V	0.7568	likely_pathogenic	0.8272	pathogenic	-0.089	Destabilizing	0.984	D	0.603	neutral	D	0.689080861	None	None	N
D/W	0.9795	likely_pathogenic	0.986	pathogenic	0.025	Stabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
D/Y	0.6162	likely_pathogenic	0.6512	pathogenic	0.029	Stabilizing	0.995	D	0.617	neutral	D	0.735062655	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.