TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9908	29947;29948;29949	chr2:178704750;178704749;178704748	chr2:179569477;179569476;179569475
N2AB	9591	28996;28997;28998	chr2:178704750;178704749;178704748	chr2:179569477;179569476;179569475
N2A	8664	26215;26216;26217	chr2:178704750;178704749;178704748	chr2:179569477;179569476;179569475
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-84
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3471
• 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
N/S	None	None	0.334	None	0.385	0.168	0.128392430309	gnomAD-4.0.0	1.59983E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8608E-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
N/A	0.8939	likely_pathogenic	0.7897	pathogenic	-0.508	Destabilizing	0.617	D	0.397	neutral	None	None	None	None	N
N/C	0.9508	likely_pathogenic	0.9117	pathogenic	0.27	Stabilizing	0.992	D	0.436	neutral	None	None	None	None	N
N/D	0.2976	likely_benign	0.2298	benign	0.182	Stabilizing	0.001	N	0.096	neutral	None	None	None	None	N
N/E	0.9038	likely_pathogenic	0.8277	pathogenic	0.174	Stabilizing	0.25	N	0.348	neutral	None	None	None	None	N
N/F	0.9826	likely_pathogenic	0.9655	pathogenic	-0.738	Destabilizing	0.739	D	0.456	neutral	None	None	None	None	N
N/G	0.879	likely_pathogenic	0.7571	pathogenic	-0.721	Destabilizing	0.4	N	0.349	neutral	None	None	None	None	N
N/H	0.6906	likely_pathogenic	0.5114	ambiguous	-0.656	Destabilizing	0.81	D	0.409	neutral	None	None	None	None	N
N/I	0.9256	likely_pathogenic	0.8782	pathogenic	-0.023	Destabilizing	0.81	D	0.452	neutral	None	None	None	None	N
N/K	0.9516	likely_pathogenic	0.8903	pathogenic	0.066	Stabilizing	0.549	D	0.325	neutral	None	None	None	None	N
N/L	0.9214	likely_pathogenic	0.8597	pathogenic	-0.023	Destabilizing	0.447	N	0.457	neutral	None	None	None	None	N
N/M	0.9378	likely_pathogenic	0.879	pathogenic	0.313	Stabilizing	0.992	D	0.407	neutral	None	None	None	None	N
N/P	0.9265	likely_pathogenic	0.8802	pathogenic	-0.156	Destabilizing	0.92	D	0.431	neutral	None	None	None	None	N
N/Q	0.9407	likely_pathogenic	0.8784	pathogenic	-0.41	Destabilizing	0.92	D	0.391	neutral	None	None	None	None	N
N/R	0.9669	likely_pathogenic	0.9361	pathogenic	0.105	Stabilizing	0.92	D	0.393	neutral	None	None	None	None	N
N/S	0.3923	ambiguous	0.2443	benign	-0.265	Destabilizing	0.334	N	0.385	neutral	None	None	None	None	N
N/T	0.7328	likely_pathogenic	0.562	ambiguous	-0.109	Destabilizing	0.712	D	0.329	neutral	None	None	None	None	N
N/V	0.9343	likely_pathogenic	0.8841	pathogenic	-0.156	Destabilizing	0.85	D	0.458	neutral	None	None	None	None	N
N/W	0.9936	likely_pathogenic	0.9883	pathogenic	-0.645	Destabilizing	0.977	D	0.452	neutral	None	None	None	None	N
N/Y	0.7871	likely_pathogenic	0.6698	pathogenic	-0.405	Destabilizing	0.004	N	0.273	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.