TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5461	16606;16607;16608	chr2:178732680;178732679;178732678	chr2:179597407;179597406;179597405
N2AB	5144	15655;15656;15657	chr2:178732680;178732679;178732678	chr2:179597407;179597406;179597405
N2A	4217	12874;12875;12876	chr2:178732680;178732679;178732678	chr2:179597407;179597406;179597405
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-38
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1662
• 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
V/A	None	None	None	D	0.135	0.28	0.475192790171	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
V/I	rs749477796	-0.439	None	N	0.154	0.22	0.365892764245	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.15E-06	0
V/I	rs749477796	-0.439	None	N	0.154	0.22	0.365892764245	gnomAD-4.0.0	3.44203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.51481E-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
V/A	0.129	likely_benign	0.1449	benign	-1.823	Destabilizing	None	N	0.135	neutral	D	0.53837215	None	None	N
V/C	0.6263	likely_pathogenic	0.6819	pathogenic	-1.275	Destabilizing	0.824	D	0.567	neutral	None	None	None	None	N
V/D	0.3687	ambiguous	0.4814	ambiguous	-1.983	Destabilizing	0.317	N	0.641	neutral	D	0.545145153	None	None	N
V/E	0.3033	likely_benign	0.3985	ambiguous	-1.835	Destabilizing	0.149	N	0.592	neutral	None	None	None	None	N
V/F	0.1693	likely_benign	0.2128	benign	-1.085	Destabilizing	0.188	N	0.626	neutral	D	0.551132634	None	None	N
V/G	0.2147	likely_benign	0.2605	benign	-2.296	Highly Destabilizing	0.062	N	0.577	neutral	D	0.526533919	None	None	N
V/H	0.581	likely_pathogenic	0.6833	pathogenic	-1.955	Destabilizing	0.935	D	0.579	neutral	None	None	None	None	N
V/I	0.0763	likely_benign	0.0794	benign	-0.548	Destabilizing	None	N	0.154	neutral	N	0.495397383	None	None	N
V/K	0.4321	ambiguous	0.5446	ambiguous	-1.621	Destabilizing	0.149	N	0.589	neutral	None	None	None	None	N
V/L	0.1693	likely_benign	0.206	benign	-0.548	Destabilizing	None	N	0.13	neutral	N	0.49971625	None	None	N
V/M	0.1422	likely_benign	0.1659	benign	-0.474	Destabilizing	0.38	N	0.533	neutral	None	None	None	None	N
V/N	0.297	likely_benign	0.3978	ambiguous	-1.714	Destabilizing	0.38	N	0.634	neutral	None	None	None	None	N
V/P	0.7986	likely_pathogenic	0.8939	pathogenic	-0.942	Destabilizing	0.555	D	0.611	neutral	None	None	None	None	N
V/Q	0.3611	ambiguous	0.4382	ambiguous	-1.657	Destabilizing	0.555	D	0.623	neutral	None	None	None	None	N
V/R	0.3522	ambiguous	0.4519	ambiguous	-1.318	Destabilizing	0.38	N	0.631	neutral	None	None	None	None	N
V/S	0.1827	likely_benign	0.2209	benign	-2.334	Highly Destabilizing	0.081	N	0.499	neutral	None	None	None	None	N
V/T	0.1498	likely_benign	0.1719	benign	-2.056	Highly Destabilizing	0.001	N	0.137	neutral	None	None	None	None	N
V/W	0.8013	likely_pathogenic	0.8735	pathogenic	-1.52	Destabilizing	0.935	D	0.585	neutral	None	None	None	None	N
V/Y	0.5012	ambiguous	0.6167	pathogenic	-1.148	Destabilizing	0.555	D	0.631	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.