TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35683	107272;107273;107274	chr2:178528704;178528703;178528702	chr2:179393431;179393430;179393429
N2AB	34042	102349;102350;102351	chr2:178528704;178528703;178528702	chr2:179393431;179393430;179393429
N2A	33115	99568;99569;99570	chr2:178528704;178528703;178528702	chr2:179393431;179393430;179393429
N2B	26618	80077;80078;80079	chr2:178528704;178528703;178528702	chr2:179393431;179393430;179393429
Novex-1	26743	80452;80453;80454	chr2:178528704;178528703;178528702	chr2:179393431;179393430;179393429
Novex-2	26810	80653;80654;80655	chr2:178528704;178528703;178528702	chr2:179393431;179393430;179393429
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-167
• Domain position: 77
• Structural Position: 163
• Q(SASA): 0.8326
• Predicted PPI site: I

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	0.027	N	0.367	0.115	0.194818534648	gnomAD-4.0.0	1.5918E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43427E-05	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	0.1324	likely_benign	0.1247	benign	-0.049	Destabilizing	None	N	0.352	neutral	N	0.457172132	None	None	I
E/C	0.8925	likely_pathogenic	0.8351	pathogenic	-0.236	Destabilizing	0.935	D	0.543	neutral	None	None	None	None	I
E/D	0.1015	likely_benign	0.0709	benign	-0.35	Destabilizing	0.052	N	0.368	neutral	N	0.46046594	None	None	I
E/F	0.7512	likely_pathogenic	0.6744	pathogenic	-0.034	Destabilizing	0.791	D	0.546	neutral	None	None	None	None	I
E/G	0.1239	likely_benign	0.1124	benign	-0.165	Destabilizing	None	N	0.403	neutral	N	0.459252432	None	None	I
E/H	0.4233	ambiguous	0.3484	ambiguous	0.588	Stabilizing	0.38	N	0.469	neutral	None	None	None	None	I
E/I	0.4233	ambiguous	0.3799	ambiguous	0.201	Stabilizing	0.38	N	0.545	neutral	None	None	None	None	I
E/K	0.1423	likely_benign	0.1358	benign	0.427	Stabilizing	0.027	N	0.367	neutral	N	0.460119224	None	None	I
E/L	0.4027	ambiguous	0.3539	ambiguous	0.201	Stabilizing	0.149	N	0.525	neutral	None	None	None	None	I
E/M	0.515	ambiguous	0.4746	ambiguous	-0.022	Destabilizing	0.555	D	0.583	neutral	None	None	None	None	I
E/N	0.1978	likely_benign	0.1413	benign	0.086	Stabilizing	0.149	N	0.415	neutral	None	None	None	None	I
E/P	0.653	likely_pathogenic	0.6133	pathogenic	0.136	Stabilizing	0.555	D	0.524	neutral	None	None	None	None	I
E/Q	0.1276	likely_benign	0.1263	benign	0.111	Stabilizing	None	N	0.283	neutral	N	0.416925807	None	None	I
E/R	0.2535	likely_benign	0.2312	benign	0.666	Stabilizing	0.081	N	0.418	neutral	None	None	None	None	I
E/S	0.1754	likely_benign	0.1468	benign	-0.024	Destabilizing	0.035	N	0.373	neutral	None	None	None	None	I
E/T	0.2113	likely_benign	0.1894	benign	0.086	Stabilizing	0.149	N	0.475	neutral	None	None	None	None	I
E/V	0.2504	likely_benign	0.2316	benign	0.136	Stabilizing	0.062	N	0.549	neutral	N	0.45734549	None	None	I
E/W	0.8451	likely_pathogenic	0.796	pathogenic	0.029	Stabilizing	0.935	D	0.549	neutral	None	None	None	None	I
E/Y	0.5529	ambiguous	0.443	ambiguous	0.19	Stabilizing	0.555	D	0.571	neutral	None	None	None	None	I

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.