TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26235	78928;78929;78930	chr2:178567429;178567428;178567427	chr2:179432156;179432155;179432154
N2AB	24594	74005;74006;74007	chr2:178567429;178567428;178567427	chr2:179432156;179432155;179432154
N2A	23667	71224;71225;71226	chr2:178567429;178567428;178567427	chr2:179432156;179432155;179432154
N2B	17170	51733;51734;51735	chr2:178567429;178567428;178567427	chr2:179432156;179432155;179432154
Novex-1	17295	52108;52109;52110	chr2:178567429;178567428;178567427	chr2:179432156;179432155;179432154
Novex-2	17362	52309;52310;52311	chr2:178567429;178567428;178567427	chr2:179432156;179432155;179432154
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-137
• Domain position: 43
• Structural Position: 69
• Q(SASA): 0.7467
• 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
E/Q	rs1695984178	None	0.983	N	0.573	0.175	0.299086750705	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs1695984178	None	0.983	N	0.573	0.175	0.299086750705	gnomAD-4.0.0	1.97254E-05	None	None	None	None	N	None	7.23624E-05	0	None	0	0	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
E/A	0.1304	likely_benign	0.1187	benign	-0.003	Destabilizing	0.805	D	0.573	neutral	N	0.501235127	None	None	N
E/C	0.7546	likely_pathogenic	0.7034	pathogenic	-0.214	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
E/D	0.1402	likely_benign	0.1222	benign	-0.268	Destabilizing	0.892	D	0.503	neutral	N	0.519879603	None	None	N
E/F	0.6607	likely_pathogenic	0.6093	pathogenic	-0.029	Destabilizing	0.987	D	0.672	neutral	None	None	None	None	N
E/G	0.1398	likely_benign	0.1261	benign	-0.126	Destabilizing	0.892	D	0.56	neutral	N	0.51079876	None	None	N
E/H	0.3847	ambiguous	0.343	ambiguous	0.573	Stabilizing	0.999	D	0.598	neutral	None	None	None	None	N
E/I	0.2674	likely_benign	0.2333	benign	0.265	Stabilizing	0.975	D	0.686	prob.neutral	None	None	None	None	N
E/K	0.1085	likely_benign	0.1031	benign	0.389	Stabilizing	0.892	D	0.564	neutral	N	0.485110882	None	None	N
E/L	0.2934	likely_benign	0.2578	benign	0.265	Stabilizing	0.95	D	0.613	neutral	None	None	None	None	N
E/M	0.36	ambiguous	0.3287	benign	0.001	Stabilizing	0.999	D	0.623	neutral	None	None	None	None	N
E/N	0.2516	likely_benign	0.221	benign	0.167	Stabilizing	0.975	D	0.606	neutral	None	None	None	None	N
E/P	0.3887	ambiguous	0.3405	ambiguous	0.194	Stabilizing	0.987	D	0.661	neutral	None	None	None	None	N
E/Q	0.122	likely_benign	0.1141	benign	0.178	Stabilizing	0.983	D	0.573	neutral	N	0.521610399	None	None	N
E/R	0.1863	likely_benign	0.1747	benign	0.647	Stabilizing	0.975	D	0.628	neutral	None	None	None	None	N
E/S	0.1639	likely_benign	0.1487	benign	0.012	Stabilizing	0.845	D	0.555	neutral	None	None	None	None	N
E/T	0.1514	likely_benign	0.138	benign	0.118	Stabilizing	0.033	N	0.346	neutral	None	None	None	None	N
E/V	0.1542	likely_benign	0.1384	benign	0.194	Stabilizing	0.805	D	0.562	neutral	N	0.50343007	None	None	N
E/W	0.8443	likely_pathogenic	0.8091	pathogenic	0.017	Stabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/Y	0.5859	likely_pathogenic	0.5265	ambiguous	0.195	Stabilizing	0.996	D	0.643	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.