TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19199	57820;57821;57822	chr2:178595759;178595758;178595757	chr2:179460486;179460485;179460484
N2AB	17558	52897;52898;52899	chr2:178595759;178595758;178595757	chr2:179460486;179460485;179460484
N2A	16631	50116;50117;50118	chr2:178595759;178595758;178595757	chr2:179460486;179460485;179460484
N2B	10134	30625;30626;30627	chr2:178595759;178595758;178595757	chr2:179460486;179460485;179460484
Novex-1	10259	31000;31001;31002	chr2:178595759;178595758;178595757	chr2:179460486;179460485;179460484
Novex-2	10326	31201;31202;31203	chr2:178595759;178595758;178595757	chr2:179460486;179460485;179460484
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-27
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.4399
• 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/K	None	None	0.024	N	0.274	0.204	0.239901079897	gnomAD-4.0.0	1.60333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87469E-06	0	0
E/V	rs2051391133	None	0.106	N	0.428	0.253	0.31077124679	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/V	rs2051391133	None	0.106	N	0.428	0.253	0.31077124679	gnomAD-4.0.0	6.5767E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47063E-05	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	0.1775	likely_benign	0.2271	benign	-0.651	Destabilizing	0.024	N	0.343	neutral	N	0.472189152	None	None	N
E/C	0.7828	likely_pathogenic	0.8578	pathogenic	-0.003	Destabilizing	0.864	D	0.328	neutral	None	None	None	None	N
E/D	0.0486	likely_benign	0.0594	benign	-0.559	Destabilizing	None	N	0.057	neutral	N	0.377084047	None	None	N
E/F	0.7063	likely_pathogenic	0.8138	pathogenic	-0.628	Destabilizing	0.628	D	0.378	neutral	None	None	None	None	N
E/G	0.1487	likely_benign	0.2076	benign	-0.88	Destabilizing	0.024	N	0.306	neutral	N	0.463761669	None	None	N
E/H	0.4224	ambiguous	0.5154	ambiguous	-0.725	Destabilizing	0.356	N	0.355	neutral	None	None	None	None	N
E/I	0.4414	ambiguous	0.5278	ambiguous	-0.069	Destabilizing	0.356	N	0.403	neutral	None	None	None	None	N
E/K	0.2542	likely_benign	0.3106	benign	0.118	Stabilizing	0.024	N	0.274	neutral	N	0.453083316	None	None	N
E/L	0.4594	ambiguous	0.5669	pathogenic	-0.069	Destabilizing	0.072	N	0.436	neutral	None	None	None	None	N
E/M	0.5527	ambiguous	0.631	pathogenic	0.315	Stabilizing	0.864	D	0.315	neutral	None	None	None	None	N
E/N	0.1287	likely_benign	0.1794	benign	-0.164	Destabilizing	0.016	N	0.249	neutral	None	None	None	None	N
E/P	0.8738	likely_pathogenic	0.9269	pathogenic	-0.243	Destabilizing	0.136	N	0.401	neutral	None	None	None	None	N
E/Q	0.2023	likely_benign	0.2309	benign	-0.143	Destabilizing	0.055	N	0.289	neutral	N	0.476498893	None	None	N
E/R	0.3783	ambiguous	0.4547	ambiguous	0.193	Stabilizing	0.072	N	0.355	neutral	None	None	None	None	N
E/S	0.1484	likely_benign	0.1925	benign	-0.362	Destabilizing	0.016	N	0.295	neutral	None	None	None	None	N
E/T	0.1759	likely_benign	0.2398	benign	-0.176	Destabilizing	0.072	N	0.335	neutral	None	None	None	None	N
E/V	0.2858	likely_benign	0.3585	ambiguous	-0.243	Destabilizing	0.106	N	0.428	neutral	N	0.513843773	None	None	N
E/W	0.8974	likely_pathogenic	0.936	pathogenic	-0.476	Destabilizing	0.864	D	0.417	neutral	None	None	None	None	N
E/Y	0.4844	ambiguous	0.6059	pathogenic	-0.384	Destabilizing	0.628	D	0.362	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.