TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5873	17842;17843;17844	chr2:178731048;178731047;178731046	chr2:179595775;179595774;179595773
N2AB	5556	16891;16892;16893	chr2:178731048;178731047;178731046	chr2:179595775;179595774;179595773
N2A	4629	14110;14111;14112	chr2:178731048;178731047;178731046	chr2:179595775;179595774;179595773
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-42
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.4977
• 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	rs2080389838	None	0.047	N	0.285	0.158	0.464098490096	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	6.33553E-05	0	None	0	0	None	0	0	0	0	0
V/F	None	None	0.002	N	0.393	0.24	0.608446283964	gnomAD-4.0.0	6.84245E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	0
V/I	None	None	0.002	N	0.251	0.074	0.333651784274	gnomAD-4.0.0	1.36849E-06	None	None	None	None	N	None	2.98972E-05	0	None	0	0	None	0	0	8.99509E-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
V/A	0.1806	likely_benign	0.1834	benign	-0.511	Destabilizing	0.047	N	0.285	neutral	N	0.504640792	None	None	N
V/C	0.7158	likely_pathogenic	0.719	pathogenic	-0.672	Destabilizing	0.983	D	0.502	neutral	None	None	None	None	N
V/D	0.3373	likely_benign	0.3741	ambiguous	0.096	Stabilizing	0.351	N	0.569	neutral	N	0.495079946	None	None	N
V/E	0.2931	likely_benign	0.3061	benign	0.008	Stabilizing	0.418	N	0.554	neutral	None	None	None	None	N
V/F	0.1293	likely_benign	0.1284	benign	-0.584	Destabilizing	0.002	N	0.393	neutral	N	0.443728406	None	None	N
V/G	0.2451	likely_benign	0.2702	benign	-0.677	Destabilizing	0.002	N	0.471	neutral	N	0.49838961	None	None	N
V/H	0.4825	ambiguous	0.4943	ambiguous	-0.232	Destabilizing	0.983	D	0.561	neutral	None	None	None	None	N
V/I	0.0765	likely_benign	0.0728	benign	-0.216	Destabilizing	0.002	N	0.251	neutral	N	0.459255219	None	None	N
V/K	0.3214	likely_benign	0.3245	benign	-0.38	Destabilizing	0.418	N	0.559	neutral	None	None	None	None	N
V/L	0.1912	likely_benign	0.1695	benign	-0.216	Destabilizing	0.037	N	0.349	neutral	N	0.470664291	None	None	N
V/M	0.1209	likely_benign	0.1162	benign	-0.305	Destabilizing	0.716	D	0.512	neutral	None	None	None	None	N
V/N	0.253	likely_benign	0.2617	benign	-0.176	Destabilizing	0.418	N	0.567	neutral	None	None	None	None	N
V/P	0.8113	likely_pathogenic	0.7876	pathogenic	-0.278	Destabilizing	0.836	D	0.56	neutral	None	None	None	None	N
V/Q	0.2851	likely_benign	0.293	benign	-0.364	Destabilizing	0.836	D	0.561	neutral	None	None	None	None	N
V/R	0.2732	likely_benign	0.2841	benign	0.051	Stabilizing	0.836	D	0.573	neutral	None	None	None	None	N
V/S	0.2043	likely_benign	0.2149	benign	-0.635	Destabilizing	0.012	N	0.435	neutral	None	None	None	None	N
V/T	0.1738	likely_benign	0.1783	benign	-0.613	Destabilizing	0.01	N	0.247	neutral	None	None	None	None	N
V/W	0.7671	likely_pathogenic	0.7437	pathogenic	-0.676	Destabilizing	0.983	D	0.563	neutral	None	None	None	None	N
V/Y	0.4552	ambiguous	0.4656	ambiguous	-0.364	Destabilizing	0.557	D	0.523	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.