TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9447	28564;28565;28566	chr2:178710758;178710757;178710756	chr2:179575485;179575484;179575483
N2AB	9130	27613;27614;27615	chr2:178710758;178710757;178710756	chr2:179575485;179575484;179575483
N2A	8203	24832;24833;24834	chr2:178710758;178710757;178710756	chr2:179575485;179575484;179575483
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-80
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.8486
• 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
Y/C	None	None	0.006	None	0.419	0.234	0.257292322809	gnomAD-4.0.0	1.591E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85778E-06	0	0
Y/H	rs1051050691	None	0.927	None	0.581	0.327	0.416707687347	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
Y/H	rs1051050691	None	0.927	None	0.581	0.327	0.416707687347	gnomAD-4.0.0	4.10499E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49711E-06	0	1.6564E-05

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
Y/A	0.43	ambiguous	0.6564	pathogenic	-1.63	Destabilizing	0.495	N	0.573	neutral	None	None	None	None	N
Y/C	0.1157	likely_benign	0.204	benign	-0.536	Destabilizing	0.006	N	0.419	neutral	None	None	None	None	N
Y/D	0.3103	likely_benign	0.5597	ambiguous	0.353	Stabilizing	0.863	D	0.603	neutral	None	None	None	None	N
Y/E	0.6497	likely_pathogenic	0.8565	pathogenic	0.388	Stabilizing	0.543	D	0.615	neutral	None	None	None	None	N
Y/F	0.0832	likely_benign	0.0872	benign	-0.785	Destabilizing	0.002	N	0.26	neutral	None	None	None	None	N
Y/G	0.4118	ambiguous	0.6543	pathogenic	-1.893	Destabilizing	0.704	D	0.589	neutral	None	None	None	None	N
Y/H	0.1775	likely_benign	0.3354	benign	-0.471	Destabilizing	0.927	D	0.581	neutral	None	None	None	None	N
Y/I	0.3306	likely_benign	0.5175	ambiguous	-0.891	Destabilizing	0.543	D	0.559	neutral	None	None	None	None	N
Y/K	0.6158	likely_pathogenic	0.8555	pathogenic	-0.495	Destabilizing	0.543	D	0.611	neutral	None	None	None	None	N
Y/L	0.2968	likely_benign	0.4529	ambiguous	-0.891	Destabilizing	0.329	N	0.521	neutral	None	None	None	None	N
Y/M	0.5134	ambiguous	0.6904	pathogenic	-0.582	Destabilizing	0.944	D	0.591	neutral	None	None	None	None	N
Y/N	0.1939	likely_benign	0.3421	ambiguous	-0.686	Destabilizing	0.863	D	0.608	neutral	None	None	None	None	N
Y/P	0.7652	likely_pathogenic	0.9211	pathogenic	-1.124	Destabilizing	0.944	D	0.609	neutral	None	None	None	None	N
Y/Q	0.4434	ambiguous	0.7415	pathogenic	-0.65	Destabilizing	0.069	N	0.369	neutral	None	None	None	None	N
Y/R	0.417	ambiguous	0.7023	pathogenic	-0.092	Destabilizing	0.807	D	0.606	neutral	None	None	None	None	N
Y/S	0.1629	likely_benign	0.2877	benign	-1.291	Destabilizing	0.642	D	0.596	neutral	None	None	None	None	N
Y/T	0.3232	likely_benign	0.5292	ambiguous	-1.161	Destabilizing	0.704	D	0.601	neutral	None	None	None	None	N
Y/V	0.2646	likely_benign	0.3973	ambiguous	-1.124	Destabilizing	0.704	D	0.534	neutral	None	None	None	None	N
Y/W	0.3631	ambiguous	0.4704	ambiguous	-0.584	Destabilizing	0.981	D	0.59	neutral	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.