TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5190	15793;15794;15795	chr2:178733821;178733820;178733819	chr2:179598548;179598547;179598546
N2AB	4873	14842;14843;14844	chr2:178733821;178733820;178733819	chr2:179598548;179598547;179598546
N2A	3946	12061;12062;12063	chr2:178733821;178733820;178733819	chr2:179598548;179598547;179598546
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-35
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1637
• 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
A/S	None	None	0.201	N	0.517	0.126	0.373897652646	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.5082	ambiguous	0.569	pathogenic	-0.809	Destabilizing	0.92	D	0.536	neutral	None	None	None	None	N
A/D	0.3386	likely_benign	0.3996	ambiguous	-0.964	Destabilizing	0.896	D	0.577	neutral	N	0.505913929	None	None	N
A/E	0.2299	likely_benign	0.2611	benign	-0.932	Destabilizing	0.766	D	0.539	neutral	None	None	None	None	N
A/F	0.3017	likely_benign	0.361	ambiguous	-0.698	Destabilizing	0.85	D	0.571	neutral	None	None	None	None	N
A/G	0.1756	likely_benign	0.216	benign	-1.106	Destabilizing	0.712	D	0.499	neutral	N	0.512068058	None	None	N
A/H	0.4818	ambiguous	0.5351	ambiguous	-1.316	Destabilizing	0.992	D	0.565	neutral	None	None	None	None	N
A/I	0.1657	likely_benign	0.2084	benign	-0.038	Destabilizing	0.103	N	0.503	neutral	None	None	None	None	N
A/K	0.428	ambiguous	0.4751	ambiguous	-1.003	Destabilizing	0.617	D	0.541	neutral	None	None	None	None	N
A/L	0.1554	likely_benign	0.1859	benign	-0.038	Destabilizing	0.25	N	0.498	neutral	None	None	None	None	N
A/M	0.1719	likely_benign	0.2047	benign	-0.137	Destabilizing	0.85	D	0.565	neutral	None	None	None	None	N
A/N	0.2382	likely_benign	0.2918	benign	-0.836	Destabilizing	0.92	D	0.585	neutral	None	None	None	None	N
A/P	0.6043	likely_pathogenic	0.7341	pathogenic	-0.244	Destabilizing	0.963	D	0.58	neutral	N	0.507787521	None	None	N
A/Q	0.3166	likely_benign	0.349	ambiguous	-0.883	Destabilizing	0.972	D	0.575	neutral	None	None	None	None	N
A/R	0.403	ambiguous	0.4274	ambiguous	-0.837	Destabilizing	0.92	D	0.589	neutral	None	None	None	None	N
A/S	0.0938	likely_benign	0.1011	benign	-1.272	Destabilizing	0.201	N	0.517	neutral	N	0.474008613	None	None	N
A/T	0.0762	likely_benign	0.082	benign	-1.133	Destabilizing	0.007	N	0.167	neutral	N	0.428186714	None	None	N
A/V	0.0926	likely_benign	0.1084	benign	-0.244	Destabilizing	0.002	N	0.167	neutral	N	0.444069366	None	None	N
A/W	0.7337	likely_pathogenic	0.7856	pathogenic	-1.154	Destabilizing	0.992	D	0.632	neutral	None	None	None	None	N
A/Y	0.4415	ambiguous	0.5154	ambiguous	-0.68	Destabilizing	0.92	D	0.57	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.