TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27734	83425;83426;83427	chr2:178562932;178562931;178562930	chr2:179427659;179427658;179427657
N2AB	26093	78502;78503;78504	chr2:178562932;178562931;178562930	chr2:179427659;179427658;179427657
N2A	25166	75721;75722;75723	chr2:178562932;178562931;178562930	chr2:179427659;179427658;179427657
N2B	18669	56230;56231;56232	chr2:178562932;178562931;178562930	chr2:179427659;179427658;179427657
Novex-1	18794	56605;56606;56607	chr2:178562932;178562931;178562930	chr2:179427659;179427658;179427657
Novex-2	18861	56806;56807;56808	chr2:178562932;178562931;178562930	chr2:179427659;179427658;179427657
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-141
• Domain position: 59
• Structural Position: 141
• Q(SASA): 0.7768
• Predicted PPI site: I

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/N	None	None	0.983	N	0.479	0.339	0.403896168776	gnomAD-4.0.0	1.59171E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85861E-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	0.4221	ambiguous	0.4201	ambiguous	-0.398	Destabilizing	0.892	D	0.515	neutral	N	0.515068429	None	None	I
D/C	0.8868	likely_pathogenic	0.8874	pathogenic	-0.024	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	I
D/E	0.2426	likely_benign	0.2485	benign	-0.647	Destabilizing	0.099	N	0.297	neutral	N	0.437511723	None	None	I
D/F	0.9395	likely_pathogenic	0.9413	pathogenic	-0.431	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	I
D/G	0.2869	likely_benign	0.2853	benign	-0.672	Destabilizing	0.892	D	0.535	neutral	N	0.500928483	None	None	I
D/H	0.605	likely_pathogenic	0.616	pathogenic	-0.733	Destabilizing	0.999	D	0.525	neutral	N	0.521226397	None	None	I
D/I	0.8687	likely_pathogenic	0.8743	pathogenic	0.296	Stabilizing	0.987	D	0.644	neutral	None	None	None	None	I
D/K	0.6989	likely_pathogenic	0.7074	pathogenic	-0.035	Destabilizing	0.975	D	0.525	neutral	None	None	None	None	I
D/L	0.8131	likely_pathogenic	0.8157	pathogenic	0.296	Stabilizing	0.975	D	0.646	neutral	None	None	None	None	I
D/M	0.9226	likely_pathogenic	0.9237	pathogenic	0.682	Stabilizing	0.999	D	0.608	neutral	None	None	None	None	I
D/N	0.1892	likely_benign	0.1925	benign	-0.316	Destabilizing	0.983	D	0.479	neutral	N	0.504102074	None	None	I
D/P	0.6792	likely_pathogenic	0.6491	pathogenic	0.089	Stabilizing	0.073	N	0.346	neutral	None	None	None	None	I
D/Q	0.5845	likely_pathogenic	0.5965	pathogenic	-0.271	Destabilizing	0.975	D	0.519	neutral	None	None	None	None	I
D/R	0.7256	likely_pathogenic	0.7384	pathogenic	-0.022	Destabilizing	0.975	D	0.571	neutral	None	None	None	None	I
D/S	0.2482	likely_benign	0.2478	benign	-0.513	Destabilizing	0.916	D	0.481	neutral	None	None	None	None	I
D/T	0.5357	ambiguous	0.5384	ambiguous	-0.297	Destabilizing	0.975	D	0.514	neutral	None	None	None	None	I
D/V	0.6955	likely_pathogenic	0.7006	pathogenic	0.089	Stabilizing	0.983	D	0.641	neutral	D	0.536483851	None	None	I
D/W	0.9794	likely_pathogenic	0.9815	pathogenic	-0.35	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	I
D/Y	0.6692	likely_pathogenic	0.6777	pathogenic	-0.2	Destabilizing	0.999	D	0.609	neutral	D	0.530384598	None	None	I

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.