TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28466	85621;85622;85623	chr2:178560736;178560735;178560734	chr2:179425463;179425462;179425461
N2AB	26825	80698;80699;80700	chr2:178560736;178560735;178560734	chr2:179425463;179425462;179425461
N2A	25898	77917;77918;77919	chr2:178560736;178560735;178560734	chr2:179425463;179425462;179425461
N2B	19401	58426;58427;58428	chr2:178560736;178560735;178560734	chr2:179425463;179425462;179425461
Novex-1	19526	58801;58802;58803	chr2:178560736;178560735;178560734	chr2:179425463;179425462;179425461
Novex-2	19593	59002;59003;59004	chr2:178560736;178560735;178560734	chr2:179425463;179425462;179425461
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: Fn3-95
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.5169
• 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/D	rs758571306	-0.636	0.999	N	0.48	0.169	0.377976839388	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/K	rs878880701	None	0.999	N	0.568	0.381	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/K	rs878880701	None	0.999	N	0.568	0.381	None	gnomAD-4.0.0	3.42126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59782E-06	0	1.65662E-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
E/A	0.3726	ambiguous	0.3795	ambiguous	-0.788	Destabilizing	0.999	D	0.648	neutral	N	0.513131697	None	None	N
E/C	0.9471	likely_pathogenic	0.9566	pathogenic	-0.218	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/D	0.267	likely_benign	0.2614	benign	-0.672	Destabilizing	0.999	D	0.48	neutral	N	0.492638995	None	None	N
E/F	0.9283	likely_pathogenic	0.9371	pathogenic	-0.511	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
E/G	0.2193	likely_benign	0.2387	benign	-1.055	Destabilizing	1.0	D	0.661	neutral	N	0.476039593	None	None	N
E/H	0.7447	likely_pathogenic	0.7706	pathogenic	-0.572	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
E/I	0.7765	likely_pathogenic	0.7962	pathogenic	-0.087	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/K	0.2263	likely_benign	0.2667	benign	-0.081	Destabilizing	0.999	D	0.568	neutral	N	0.4716715	None	None	N
E/L	0.7079	likely_pathogenic	0.7314	pathogenic	-0.087	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/M	0.7431	likely_pathogenic	0.763	pathogenic	0.25	Stabilizing	1.0	D	0.601	neutral	None	None	None	None	N
E/N	0.4878	ambiguous	0.4784	ambiguous	-0.477	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/P	0.9459	likely_pathogenic	0.9671	pathogenic	-0.3	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/Q	0.2234	likely_benign	0.2383	benign	-0.426	Destabilizing	1.0	D	0.602	neutral	N	0.481977848	None	None	N
E/R	0.3651	ambiguous	0.4233	ambiguous	0.123	Stabilizing	1.0	D	0.658	neutral	None	None	None	None	N
E/S	0.3882	ambiguous	0.3879	ambiguous	-0.691	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
E/T	0.4366	ambiguous	0.4466	ambiguous	-0.472	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/V	0.5338	ambiguous	0.5591	ambiguous	-0.3	Destabilizing	1.0	D	0.683	prob.neutral	N	0.502146018	None	None	N
E/W	0.9469	likely_pathogenic	0.9604	pathogenic	-0.271	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/Y	0.8418	likely_pathogenic	0.8704	pathogenic	-0.253	Destabilizing	1.0	D	0.636	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.