TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24631	74116;74117;74118	chr2:178572241;178572240;178572239	chr2:179436968;179436967;179436966
N2AB	22990	69193;69194;69195	chr2:178572241;178572240;178572239	chr2:179436968;179436967;179436966
N2A	22063	66412;66413;66414	chr2:178572241;178572240;178572239	chr2:179436968;179436967;179436966
N2B	15566	46921;46922;46923	chr2:178572241;178572240;178572239	chr2:179436968;179436967;179436966
Novex-1	15691	47296;47297;47298	chr2:178572241;178572240;178572239	chr2:179436968;179436967;179436966
Novex-2	15758	47497;47498;47499	chr2:178572241;178572240;178572239	chr2:179436968;179436967;179436966
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-67
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.2773
• 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
N/I	None	None	0.989	N	0.597	0.336	0.608896402506	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	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
N/A	0.3232	likely_benign	0.3197	benign	-0.665	Destabilizing	0.532	D	0.501	neutral	None	None	None	None	N
N/C	0.3672	ambiguous	0.3547	ambiguous	0.195	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	N
N/D	0.1754	likely_benign	0.1799	benign	-0.467	Destabilizing	0.841	D	0.528	neutral	N	0.471285075	None	None	N
N/E	0.4284	ambiguous	0.4541	ambiguous	-0.488	Destabilizing	0.959	D	0.486	neutral	None	None	None	None	N
N/F	0.601	likely_pathogenic	0.5722	pathogenic	-1.023	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	N
N/G	0.3498	ambiguous	0.3546	ambiguous	-0.848	Destabilizing	0.983	D	0.494	neutral	None	None	None	None	N
N/H	0.1087	likely_benign	0.1116	benign	-0.912	Destabilizing	0.998	D	0.491	neutral	N	0.483697011	None	None	N
N/I	0.442	ambiguous	0.4115	ambiguous	-0.256	Destabilizing	0.989	D	0.597	neutral	N	0.489134326	None	None	N
N/K	0.3076	likely_benign	0.3457	ambiguous	0.032	Stabilizing	0.985	D	0.485	neutral	N	0.516577434	None	None	N
N/L	0.3538	ambiguous	0.3479	ambiguous	-0.256	Destabilizing	0.97	D	0.511	neutral	None	None	None	None	N
N/M	0.3876	ambiguous	0.3915	ambiguous	0.457	Stabilizing	1.0	D	0.563	neutral	None	None	None	None	N
N/P	0.9238	likely_pathogenic	0.9249	pathogenic	-0.367	Destabilizing	0.993	D	0.566	neutral	None	None	None	None	N
N/Q	0.3225	likely_benign	0.3486	ambiguous	-0.683	Destabilizing	0.996	D	0.474	neutral	None	None	None	None	N
N/R	0.3745	ambiguous	0.3913	ambiguous	0.198	Stabilizing	0.998	D	0.466	neutral	None	None	None	None	N
N/S	0.0922	likely_benign	0.0948	benign	-0.348	Destabilizing	0.172	N	0.191	neutral	N	0.433073403	None	None	N
N/T	0.1287	likely_benign	0.1326	benign	-0.224	Destabilizing	0.044	N	0.107	neutral	N	0.420794752	None	None	N
N/V	0.4115	ambiguous	0.3918	ambiguous	-0.367	Destabilizing	0.905	D	0.491	neutral	None	None	None	None	N
N/W	0.8318	likely_pathogenic	0.8191	pathogenic	-0.883	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
N/Y	0.2119	likely_benign	0.2018	benign	-0.633	Destabilizing	0.999	D	0.579	neutral	N	0.489134326	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.