TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3947	12064;12065;12066	chr2:178741394;178741393;178741392	chr2:179606121;179606120;179606119
N2AB	3630	11113;11114;11115	chr2:178741394;178741393;178741392	chr2:179606121;179606120;179606119
N2A	None	None	chr2:None	chr2:None
N2B	3584	10975;10976;10977	chr2:178741394;178741393;178741392	chr2:179606121;179606120;179606119
Novex-1	3709	11350;11351;11352	chr2:178741394;178741393;178741392	chr2:179606121;179606120;179606119
Novex-2	3776	11551;11552;11553	chr2:178741394;178741393;178741392	chr2:179606121;179606120;179606119
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-28
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2031
• 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/M	None	None	0.171	N	0.376	0.078	None	gnomAD-4.0.0	1.59106E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-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	0.3115	likely_benign	0.3254	benign	-1.671	Destabilizing	None	N	0.156	neutral	None	None	None	None	N
I/C	0.6392	likely_pathogenic	0.6442	pathogenic	-0.787	Destabilizing	0.356	N	0.37	neutral	None	None	None	None	N
I/D	0.7647	likely_pathogenic	0.7678	pathogenic	-1.132	Destabilizing	0.072	N	0.523	neutral	None	None	None	None	N
I/E	0.5839	likely_pathogenic	0.5946	pathogenic	-1.075	Destabilizing	0.072	N	0.474	neutral	None	None	None	None	N
I/F	0.1931	likely_benign	0.1994	benign	-1.036	Destabilizing	0.055	N	0.334	neutral	N	0.515177549	None	None	N
I/G	0.6425	likely_pathogenic	0.6378	pathogenic	-2.045	Highly Destabilizing	0.016	N	0.369	neutral	None	None	None	None	N
I/H	0.5829	likely_pathogenic	0.5867	pathogenic	-1.318	Destabilizing	0.628	D	0.424	neutral	None	None	None	None	N
I/K	0.4348	ambiguous	0.4446	ambiguous	-1.112	Destabilizing	0.072	N	0.455	neutral	None	None	None	None	N
I/L	0.1249	likely_benign	0.1239	benign	-0.687	Destabilizing	None	N	0.059	neutral	N	0.492856004	None	None	N
I/M	0.1206	likely_benign	0.1264	benign	-0.493	Destabilizing	0.171	N	0.376	neutral	N	0.513947109	None	None	N
I/N	0.3523	ambiguous	0.3695	ambiguous	-0.964	Destabilizing	0.055	N	0.523	neutral	N	0.507003817	None	None	N
I/P	0.8599	likely_pathogenic	0.8408	pathogenic	-0.985	Destabilizing	0.136	N	0.511	neutral	None	None	None	None	N
I/Q	0.46	ambiguous	0.4715	ambiguous	-1.055	Destabilizing	0.356	N	0.535	neutral	None	None	None	None	N
I/R	0.3181	likely_benign	0.3291	benign	-0.636	Destabilizing	0.356	N	0.545	neutral	None	None	None	None	N
I/S	0.3247	likely_benign	0.3451	ambiguous	-1.585	Destabilizing	0.001	N	0.303	neutral	N	0.503273066	None	None	N
I/T	0.247	likely_benign	0.2667	benign	-1.408	Destabilizing	0.012	N	0.342	neutral	N	0.479524621	None	None	N
I/V	0.0623	likely_benign	0.0599	benign	-0.985	Destabilizing	None	N	0.057	neutral	N	0.413437524	None	None	N
I/W	0.8277	likely_pathogenic	0.8215	pathogenic	-1.204	Destabilizing	0.864	D	0.449	neutral	None	None	None	None	N
I/Y	0.5485	ambiguous	0.5645	pathogenic	-0.947	Destabilizing	0.356	N	0.465	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.