TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6158	18697;18698;18699	chr2:178729781;178729780;178729779	chr2:179594508;179594507;179594506
N2AB	5841	17746;17747;17748	chr2:178729781;178729780;178729779	chr2:179594508;179594507;179594506
N2A	4914	14965;14966;14967	chr2:178729781;178729780;178729779	chr2:179594508;179594507;179594506
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: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-45
• Domain position: 54
• Structural Position: 131
• Q(SASA): 1.0245
• 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/G	None	None	0.892	N	0.473	0.332	0.377799810692	gnomAD-4.0.0	3.18276E-06	None	None	None	None	N	None	0	0	None	0	2.77393E-05	None	0	0	2.85847E-06	0	0
D/N	rs2080068286	None	0.099	N	0.251	0.239	0.288352970974	gnomAD-4.0.0	5.47383E-06	None	None	None	None	N	None	0	0	None	0	1.76402E-04	None	0	0	8.99488E-07	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	0.1652	likely_benign	0.1855	benign	-0.05	Destabilizing	0.892	D	0.396	neutral	N	0.496562698	None	None	N
D/C	0.5797	likely_pathogenic	0.6052	pathogenic	-0.345	Destabilizing	0.999	D	0.616	neutral	None	None	None	None	N
D/E	0.154	likely_benign	0.1649	benign	-0.367	Destabilizing	0.025	N	0.285	neutral	N	0.513321777	None	None	N
D/F	0.6165	likely_pathogenic	0.6619	pathogenic	0.017	Stabilizing	0.999	D	0.535	neutral	None	None	None	None	N
D/G	0.1042	likely_benign	0.1173	benign	-0.175	Destabilizing	0.892	D	0.473	neutral	N	0.510467899	None	None	N
D/H	0.179	likely_benign	0.2049	benign	0.691	Stabilizing	0.995	D	0.455	neutral	N	0.514199654	None	None	N
D/I	0.5381	ambiguous	0.5798	pathogenic	0.221	Stabilizing	0.987	D	0.55	neutral	None	None	None	None	N
D/K	0.2494	likely_benign	0.2773	benign	0.389	Stabilizing	0.845	D	0.419	neutral	None	None	None	None	N
D/L	0.4469	ambiguous	0.4918	ambiguous	0.221	Stabilizing	0.975	D	0.552	neutral	None	None	None	None	N
D/M	0.676	likely_pathogenic	0.7094	pathogenic	-0.053	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
D/N	0.0815	likely_benign	0.0837	benign	-0.089	Destabilizing	0.099	N	0.251	neutral	N	0.46797349	None	None	N
D/P	0.6057	likely_pathogenic	0.6226	pathogenic	0.15	Stabilizing	0.987	D	0.439	neutral	None	None	None	None	N
D/Q	0.2489	likely_benign	0.2756	benign	-0.047	Destabilizing	0.95	D	0.459	neutral	None	None	None	None	N
D/R	0.2372	likely_benign	0.2746	benign	0.686	Stabilizing	0.975	D	0.491	neutral	None	None	None	None	N
D/S	0.107	likely_benign	0.1169	benign	-0.127	Destabilizing	0.916	D	0.443	neutral	None	None	None	None	N
D/T	0.2923	likely_benign	0.32	benign	-0.008	Destabilizing	0.975	D	0.417	neutral	None	None	None	None	N
D/V	0.3446	ambiguous	0.3824	ambiguous	0.15	Stabilizing	0.983	D	0.549	neutral	D	0.530582389	None	None	N
D/W	0.7836	likely_pathogenic	0.8209	pathogenic	0.103	Stabilizing	0.999	D	0.636	neutral	None	None	None	None	N
D/Y	0.2198	likely_benign	0.2438	benign	0.245	Stabilizing	0.999	D	0.536	neutral	N	0.514199654	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.