TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26666	80221;80222;80223	chr2:178566136;178566135;178566134	chr2:179430863;179430862;179430861
N2AB	25025	75298;75299;75300	chr2:178566136;178566135;178566134	chr2:179430863;179430862;179430861
N2A	24098	72517;72518;72519	chr2:178566136;178566135;178566134	chr2:179430863;179430862;179430861
N2B	17601	53026;53027;53028	chr2:178566136;178566135;178566134	chr2:179430863;179430862;179430861
Novex-1	17726	53401;53402;53403	chr2:178566136;178566135;178566134	chr2:179430863;179430862;179430861
Novex-2	17793	53602;53603;53604	chr2:178566136;178566135;178566134	chr2:179430863;179430862;179430861
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-138
• Domain position: 73
• Structural Position: 159
• Q(SASA): 0.3991
• 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/G	rs766614271	-0.76	0.967	N	0.729	0.543	0.507093260865	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.6715E-04	None	0	None	0	0	0
E/G	rs766614271	-0.76	0.967	N	0.729	0.543	0.507093260865	gnomAD-4.0.0	3.42129E-06	None	None	None	None	N	None	0	0	None	0	1.25995E-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
E/A	0.2327	likely_benign	0.2254	benign	-0.53	Destabilizing	0.805	D	0.644	neutral	N	0.49116374	None	None	N
E/C	0.8357	likely_pathogenic	0.8154	pathogenic	0.012	Stabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
E/D	0.2738	likely_benign	0.2619	benign	-0.797	Destabilizing	0.892	D	0.49	neutral	N	0.500900657	None	None	N
E/F	0.8596	likely_pathogenic	0.8339	pathogenic	-0.685	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
E/G	0.3237	likely_benign	0.3104	benign	-0.779	Destabilizing	0.967	D	0.729	prob.delet.	N	0.513017431	None	None	N
E/H	0.5485	ambiguous	0.5042	ambiguous	-0.97	Destabilizing	0.997	D	0.743	deleterious	None	None	None	None	N
E/I	0.4048	ambiguous	0.3896	ambiguous	0.107	Stabilizing	0.987	D	0.832	deleterious	None	None	None	None	N
E/K	0.252	likely_benign	0.2258	benign	-0.007	Destabilizing	0.805	D	0.593	neutral	N	0.518762095	None	None	N
E/L	0.5486	ambiguous	0.5289	ambiguous	0.107	Stabilizing	0.975	D	0.753	deleterious	None	None	None	None	N
E/M	0.5194	ambiguous	0.5078	ambiguous	0.558	Stabilizing	0.997	D	0.807	deleterious	None	None	None	None	N
E/N	0.4111	ambiguous	0.3846	ambiguous	-0.253	Destabilizing	0.975	D	0.734	prob.delet.	None	None	None	None	N
E/P	0.9923	likely_pathogenic	0.9906	pathogenic	-0.084	Destabilizing	0.987	D	0.778	deleterious	None	None	None	None	N
E/Q	0.1278	likely_benign	0.1211	benign	-0.223	Destabilizing	0.099	N	0.268	neutral	N	0.509817325	None	None	N
E/R	0.3972	ambiguous	0.3704	ambiguous	-0.031	Destabilizing	0.95	D	0.735	prob.delet.	None	None	None	None	N
E/S	0.2688	likely_benign	0.2554	benign	-0.462	Destabilizing	0.845	D	0.652	neutral	None	None	None	None	N
E/T	0.2384	likely_benign	0.2192	benign	-0.259	Destabilizing	0.975	D	0.719	prob.delet.	None	None	None	None	N
E/V	0.2257	likely_benign	0.2184	benign	-0.084	Destabilizing	0.967	D	0.784	deleterious	N	0.494063802	None	None	N
E/W	0.9452	likely_pathogenic	0.9349	pathogenic	-0.635	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
E/Y	0.7932	likely_pathogenic	0.7621	pathogenic	-0.463	Destabilizing	0.987	D	0.824	deleterious	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.