TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8253	24982;24983;24984	chr2:178718349;178718348;178718347	chr2:179583076;179583075;179583074
N2AB	7936	24031;24032;24033	chr2:178718349;178718348;178718347	chr2:179583076;179583075;179583074
N2A	7009	21250;21251;21252	chr2:178718349;178718348;178718347	chr2:179583076;179583075;179583074
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-67
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.214
• 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
I/T	rs376588656	-1.321	0.003	N	0.198	0.133	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
I/T	rs376588656	-1.321	0.003	N	0.198	0.133	None	gnomAD-4.0.0	1.59175E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	None	0	0	0	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
I/A	0.1873	likely_benign	0.1912	benign	-1.798	Destabilizing	0.061	N	0.292	neutral	None	None	None	None	N
I/C	0.5251	ambiguous	0.521	ambiguous	-0.908	Destabilizing	0.94	D	0.517	neutral	None	None	None	None	N
I/D	0.3826	ambiguous	0.3807	ambiguous	-1.149	Destabilizing	0.418	N	0.517	neutral	None	None	None	None	N
I/E	0.2914	likely_benign	0.2885	benign	-1.1	Destabilizing	0.418	N	0.502	neutral	None	None	None	None	N
I/F	0.1049	likely_benign	0.1035	benign	-1.188	Destabilizing	0.655	D	0.502	neutral	N	0.503043281	None	None	N
I/G	0.4142	ambiguous	0.4073	ambiguous	-2.17	Highly Destabilizing	0.264	N	0.487	neutral	None	None	None	None	N
I/H	0.2386	likely_benign	0.2457	benign	-1.329	Destabilizing	0.94	D	0.487	neutral	None	None	None	None	N
I/K	0.1687	likely_benign	0.189	benign	-1.11	Destabilizing	0.01	N	0.332	neutral	None	None	None	None	N
I/L	0.1058	likely_benign	0.105	benign	-0.825	Destabilizing	0.047	N	0.24	neutral	N	0.502869923	None	None	N
I/M	0.0954	likely_benign	0.0974	benign	-0.563	Destabilizing	0.655	D	0.469	neutral	N	0.484705278	None	None	N
I/N	0.1266	likely_benign	0.1318	benign	-0.993	Destabilizing	0.351	N	0.534	neutral	N	0.468583991	None	None	N
I/P	0.8608	likely_pathogenic	0.8424	pathogenic	-1.12	Destabilizing	0.593	D	0.577	neutral	None	None	None	None	N
I/Q	0.2342	likely_benign	0.2422	benign	-1.117	Destabilizing	0.716	D	0.573	neutral	None	None	None	None	N
I/R	0.1243	likely_benign	0.1362	benign	-0.552	Destabilizing	0.264	N	0.565	neutral	None	None	None	None	N
I/S	0.1269	likely_benign	0.1335	benign	-1.669	Destabilizing	0.003	N	0.299	neutral	N	0.41253592	None	None	N
I/T	0.1079	likely_benign	0.115	benign	-1.499	Destabilizing	0.003	N	0.198	neutral	N	0.419864538	None	None	N
I/V	0.0753	likely_benign	0.0762	benign	-1.12	Destabilizing	0.001	N	0.107	neutral	N	0.453577253	None	None	N
I/W	0.5945	likely_pathogenic	0.5642	pathogenic	-1.315	Destabilizing	0.983	D	0.521	neutral	None	None	None	None	N
I/Y	0.2935	likely_benign	0.2876	benign	-1.069	Destabilizing	0.836	D	0.567	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.