TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26778	80557;80558;80559	chr2:178565800;178565799;178565798	chr2:179430527;179430526;179430525
N2AB	25137	75634;75635;75636	chr2:178565800;178565799;178565798	chr2:179430527;179430526;179430525
N2A	24210	72853;72854;72855	chr2:178565800;178565799;178565798	chr2:179430527;179430526;179430525
N2B	17713	53362;53363;53364	chr2:178565800;178565799;178565798	chr2:179430527;179430526;179430525
Novex-1	17838	53737;53738;53739	chr2:178565800;178565799;178565798	chr2:179430527;179430526;179430525
Novex-2	17905	53938;53939;53940	chr2:178565800;178565799;178565798	chr2:179430527;179430526;179430525
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-82
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.345
• 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
A/D	rs1463558062	-0.433	0.186	N	0.6	0.154	0.289474373501	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
A/D	rs1463558062	-0.433	0.186	N	0.6	0.154	0.289474373501	gnomAD-4.0.0	4.10564E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39738E-06	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
A/C	0.3334	likely_benign	0.3769	ambiguous	-0.935	Destabilizing	0.823	D	0.383	neutral	None	None	None	None	N
A/D	0.8414	likely_pathogenic	0.8046	pathogenic	-1.182	Destabilizing	0.186	N	0.6	neutral	N	0.510723323	None	None	N
A/E	0.7418	likely_pathogenic	0.7047	pathogenic	-1.302	Destabilizing	0.08	N	0.535	neutral	None	None	None	None	N
A/F	0.6299	likely_pathogenic	0.5854	pathogenic	-1.226	Destabilizing	0.378	N	0.679	prob.neutral	None	None	None	None	N
A/G	0.2118	likely_benign	0.2143	benign	-0.999	Destabilizing	0.061	N	0.343	neutral	N	0.482806003	None	None	N
A/H	0.8436	likely_pathogenic	0.8381	pathogenic	-0.999	Destabilizing	0.823	D	0.652	prob.neutral	None	None	None	None	N
A/I	0.5283	ambiguous	0.4751	ambiguous	-0.677	Destabilizing	0.08	N	0.525	neutral	None	None	None	None	N
A/K	0.9275	likely_pathogenic	0.9165	pathogenic	-1.178	Destabilizing	0.08	N	0.546	neutral	None	None	None	None	N
A/L	0.4059	ambiguous	0.3636	ambiguous	-0.677	Destabilizing	0.001	N	0.337	neutral	None	None	None	None	N
A/M	0.3691	ambiguous	0.3378	benign	-0.505	Destabilizing	0.378	N	0.479	neutral	None	None	None	None	N
A/N	0.69	likely_pathogenic	0.6533	pathogenic	-0.823	Destabilizing	0.233	N	0.576	neutral	None	None	None	None	N
A/P	0.9718	likely_pathogenic	0.9676	pathogenic	-0.703	Destabilizing	0.314	N	0.54	neutral	N	0.463505379	None	None	N
A/Q	0.7282	likely_pathogenic	0.7261	pathogenic	-1.14	Destabilizing	0.378	N	0.581	neutral	None	None	None	None	N
A/R	0.8769	likely_pathogenic	0.8584	pathogenic	-0.624	Destabilizing	0.378	N	0.537	neutral	None	None	None	None	N
A/S	0.0756	likely_benign	0.0822	benign	-1.061	Destabilizing	None	N	0.108	neutral	N	0.396533813	None	None	N
A/T	0.1198	likely_benign	0.1111	benign	-1.11	Destabilizing	0.061	N	0.341	neutral	N	0.501565122	None	None	N
A/V	0.2498	likely_benign	0.2216	benign	-0.703	Destabilizing	0.061	N	0.365	neutral	N	0.477418826	None	None	N
A/W	0.9151	likely_pathogenic	0.9076	pathogenic	-1.378	Destabilizing	0.934	D	0.736	deleterious	None	None	None	None	N
A/Y	0.783	likely_pathogenic	0.7561	pathogenic	-1.066	Destabilizing	0.552	D	0.676	prob.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.