TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8564	25915;25916;25917	chr2:178715724;178715723;178715722	chr2:179580451;179580450;179580449
N2AB	8247	24964;24965;24966	chr2:178715724;178715723;178715722	chr2:179580451;179580450;179580449
N2A	7320	22183;22184;22185	chr2:178715724;178715723;178715722	chr2:179580451;179580450;179580449
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-71
• Domain position: 16
• Structural Position: 24
• Q(SASA): 0.723
• 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
D/G	rs770623711	-0.471	None	N	0.211	0.084	0.0297737177859	gnomAD-2.1.1	8.91E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.02E-05	0
D/G	rs770623711	-0.471	None	N	0.211	0.084	0.0297737177859	gnomAD-4.0.0	2.07109E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.7158E-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
D/A	0.1106	likely_benign	0.1195	benign	-0.293	Destabilizing	None	N	0.201	neutral	D	0.528133727	None	None	I
D/C	0.3734	ambiguous	0.3925	ambiguous	0.067	Stabilizing	0.112	N	0.511	neutral	None	None	None	None	I
D/E	0.1096	likely_benign	0.1218	benign	-0.383	Destabilizing	0.001	N	0.355	neutral	N	0.455809482	None	None	I
D/F	0.3517	ambiguous	0.3627	ambiguous	-0.353	Destabilizing	0.171	N	0.511	neutral	None	None	None	None	I
D/G	0.0571	likely_benign	0.0645	benign	-0.491	Destabilizing	None	N	0.211	neutral	N	0.272564452	None	None	I
D/H	0.1199	likely_benign	0.1198	benign	-0.319	Destabilizing	None	N	0.229	neutral	N	0.432049975	None	None	I
D/I	0.3208	likely_benign	0.3218	benign	0.179	Stabilizing	0.055	N	0.52	neutral	None	None	None	None	I
D/K	0.1632	likely_benign	0.1751	benign	0.206	Stabilizing	0.012	N	0.401	neutral	None	None	None	None	I
D/L	0.2268	likely_benign	0.2426	benign	0.179	Stabilizing	0.029	N	0.464	neutral	None	None	None	None	I
D/M	0.4036	ambiguous	0.4112	ambiguous	0.38	Stabilizing	0.322	N	0.518	neutral	None	None	None	None	I
D/N	0.0638	likely_benign	0.0609	benign	0.013	Stabilizing	None	N	0.165	neutral	N	0.393203585	None	None	I
D/P	0.6004	likely_pathogenic	0.6039	pathogenic	0.044	Stabilizing	0.002	N	0.469	neutral	None	None	None	None	I
D/Q	0.1555	likely_benign	0.1693	benign	0.023	Stabilizing	0.022	N	0.357	neutral	None	None	None	None	I
D/R	0.1705	likely_benign	0.1859	benign	0.321	Stabilizing	0.055	N	0.471	neutral	None	None	None	None	I
D/S	0.084	likely_benign	0.0866	benign	-0.12	Destabilizing	None	N	0.144	neutral	None	None	None	None	I
D/T	0.1696	likely_benign	0.1666	benign	0.025	Stabilizing	0.002	N	0.404	neutral	None	None	None	None	I
D/V	0.2039	likely_benign	0.2065	benign	0.044	Stabilizing	0.004	N	0.477	neutral	D	0.528480444	None	None	I
D/W	0.6062	likely_pathogenic	0.6392	pathogenic	-0.264	Destabilizing	0.828	D	0.503	neutral	None	None	None	None	I
D/Y	0.1289	likely_benign	0.1269	benign	-0.132	Destabilizing	0.072	N	0.525	neutral	N	0.510068041	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.