TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10070	30433;30434;30435	chr2:178704162;178704161;178704160	chr2:179568889;179568888;179568887
N2AB	9753	29482;29483;29484	chr2:178704162;178704161;178704160	chr2:179568889;179568888;179568887
N2A	8826	26701;26702;26703	chr2:178704162;178704161;178704160	chr2:179568889;179568888;179568887
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-85
• Domain position: 82
• Structural Position: 173
• Q(SASA): 0.4069
• 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
E/D	None	None	0.001	None	0.167	0.112	0.0401082797425	gnomAD-4.0.0	6.84234E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99433E-07	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
E/A	0.185	likely_benign	0.2144	benign	-0.707	Destabilizing	0.549	D	0.523	neutral	None	None	None	None	N
E/C	0.9072	likely_pathogenic	0.929	pathogenic	-0.425	Destabilizing	0.992	D	0.621	neutral	None	None	None	None	N
E/D	0.1137	likely_benign	0.1459	benign	-1.253	Destabilizing	0.001	N	0.167	neutral	None	None	None	None	N
E/F	0.6763	likely_pathogenic	0.729	pathogenic	-0.576	Destabilizing	0.972	D	0.625	neutral	None	None	None	None	N
E/G	0.2638	likely_benign	0.3778	ambiguous	-1.038	Destabilizing	0.549	D	0.552	neutral	None	None	None	None	N
E/H	0.4763	ambiguous	0.5538	ambiguous	-0.956	Destabilizing	0.92	D	0.58	neutral	None	None	None	None	N
E/I	0.3558	ambiguous	0.4015	ambiguous	0.18	Stabilizing	0.92	D	0.64	neutral	None	None	None	None	N
E/K	0.1947	likely_benign	0.2448	benign	-0.687	Destabilizing	0.549	D	0.526	neutral	None	None	None	None	N
E/L	0.3914	ambiguous	0.4611	ambiguous	0.18	Stabilizing	0.92	D	0.61	neutral	None	None	None	None	N
E/M	0.4611	ambiguous	0.5027	ambiguous	0.625	Stabilizing	0.992	D	0.62	neutral	None	None	None	None	N
E/N	0.2012	likely_benign	0.2537	benign	-0.975	Destabilizing	0.021	N	0.277	neutral	None	None	None	None	N
E/P	0.854	likely_pathogenic	0.9308	pathogenic	-0.093	Destabilizing	0.92	D	0.605	neutral	None	None	None	None	N
E/Q	0.1736	likely_benign	0.2017	benign	-0.879	Destabilizing	0.549	D	0.556	neutral	None	None	None	None	N
E/R	0.3151	likely_benign	0.3905	ambiguous	-0.55	Destabilizing	0.92	D	0.585	neutral	None	None	None	None	N
E/S	0.2034	likely_benign	0.2521	benign	-1.286	Destabilizing	0.447	N	0.535	neutral	None	None	None	None	N
E/T	0.2264	likely_benign	0.2592	benign	-1.02	Destabilizing	0.617	D	0.537	neutral	None	None	None	None	N
E/V	0.2121	likely_benign	0.2427	benign	-0.093	Destabilizing	0.896	D	0.615	neutral	None	None	None	None	N
E/W	0.8904	likely_pathogenic	0.9189	pathogenic	-0.505	Destabilizing	0.992	D	0.625	neutral	None	None	None	None	N
E/Y	0.5969	likely_pathogenic	0.6648	pathogenic	-0.37	Destabilizing	0.972	D	0.633	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.