TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19692	59299;59300;59301	chr2:178593045;178593044;178593043	chr2:179457772;179457771;179457770
N2AB	18051	54376;54377;54378	chr2:178593045;178593044;178593043	chr2:179457772;179457771;179457770
N2A	17124	51595;51596;51597	chr2:178593045;178593044;178593043	chr2:179457772;179457771;179457770
N2B	10627	32104;32105;32106	chr2:178593045;178593044;178593043	chr2:179457772;179457771;179457770
Novex-1	10752	32479;32480;32481	chr2:178593045;178593044;178593043	chr2:179457772;179457771;179457770
Novex-2	10819	32680;32681;32682	chr2:178593045;178593044;178593043	chr2:179457772;179457771;179457770
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-31
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.316
• 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
T/A	rs771977738	-0.593	0.425	N	0.285	0.16	0.17948927462	gnomAD-2.1.1	5.24E-05	None	None	None	None	N	None	0	3.77665E-04	None	0	0	None	0	None	0	0	0
T/A	rs771977738	-0.593	0.425	N	0.285	0.16	0.17948927462	gnomAD-4.0.0	1.09498E-05	None	None	None	None	N	None	0	3.35706E-04	None	0	0	None	0	0	8.99588E-07	0	0
T/I	rs774404108	None	0.642	N	0.345	0.175	0.240491677333	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs774404108	None	0.642	N	0.345	0.175	0.240491677333	gnomAD-4.0.0	6.57687E-06	None	None	None	None	N	None	2.41406E-05	0	None	0	0	None	0	0	0	0	0
T/K	None	-0.533	0.001	N	0.165	0.188	0.227260227426	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
T/K	None	-0.533	0.001	N	0.165	0.188	0.227260227426	gnomAD-4.0.0	2.05309E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79918E-06	0	1.65684E-05
T/R	rs774404108	-0.118	0.473	N	0.383	0.222	None	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.45E-05	0
T/R	rs774404108	-0.118	0.473	N	0.383	0.222	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
T/R	rs774404108	-0.118	0.473	N	0.383	0.222	None	gnomAD-4.0.0	1.73562E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.28891E-05	0	1.60138E-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
T/A	0.1516	likely_benign	0.1134	benign	-0.251	Destabilizing	0.425	N	0.285	neutral	N	0.438172579	None	None	N
T/C	0.4927	ambiguous	0.4427	ambiguous	-0.699	Destabilizing	0.995	D	0.317	neutral	None	None	None	None	N
T/D	0.8204	likely_pathogenic	0.7315	pathogenic	-1.975	Destabilizing	0.704	D	0.361	neutral	None	None	None	None	N
T/E	0.6436	likely_pathogenic	0.524	ambiguous	-1.933	Destabilizing	0.329	N	0.364	neutral	None	None	None	None	N
T/F	0.48	ambiguous	0.355	ambiguous	-0.688	Destabilizing	0.003	N	0.216	neutral	None	None	None	None	N
T/G	0.4924	ambiguous	0.4147	ambiguous	-0.48	Destabilizing	0.704	D	0.386	neutral	None	None	None	None	N
T/H	0.4406	ambiguous	0.3563	ambiguous	-1.009	Destabilizing	0.981	D	0.386	neutral	None	None	None	None	N
T/I	0.2529	likely_benign	0.1899	benign	0.266	Stabilizing	0.642	D	0.345	neutral	N	0.39857404	None	None	N
T/K	0.2915	likely_benign	0.221	benign	-0.468	Destabilizing	0.001	N	0.165	neutral	N	0.403233286	None	None	N
T/L	0.2226	likely_benign	0.1667	benign	0.266	Stabilizing	0.329	N	0.37	neutral	None	None	None	None	N
T/M	0.1565	likely_benign	0.1103	benign	0.483	Stabilizing	0.981	D	0.349	neutral	None	None	None	None	N
T/N	0.3641	ambiguous	0.2821	benign	-0.987	Destabilizing	0.704	D	0.289	neutral	None	None	None	None	N
T/P	0.5199	ambiguous	0.4062	ambiguous	0.124	Stabilizing	0.784	D	0.372	neutral	N	0.464359102	None	None	N
T/Q	0.3782	ambiguous	0.2985	benign	-1.221	Destabilizing	0.704	D	0.371	neutral	None	None	None	None	N
T/R	0.28	likely_benign	0.1986	benign	-0.298	Destabilizing	0.473	N	0.383	neutral	N	0.469322205	None	None	N
T/S	0.2073	likely_benign	0.1677	benign	-0.864	Destabilizing	0.425	N	0.33	neutral	N	0.459259927	None	None	N
T/V	0.1798	likely_benign	0.1421	benign	0.124	Stabilizing	0.495	N	0.292	neutral	None	None	None	None	N
T/W	0.8186	likely_pathogenic	0.7206	pathogenic	-0.885	Destabilizing	0.995	D	0.363	neutral	None	None	None	None	N
T/Y	0.4963	ambiguous	0.3718	ambiguous	-0.405	Destabilizing	0.543	D	0.392	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.