TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7034	21325;21326;21327	chr2:178724275;178724274;178724273	chr2:179589002;179589001;179589000
N2AB	6717	20374;20375;20376	chr2:178724275;178724274;178724273	chr2:179589002;179589001;179589000
N2A	5790	17593;17594;17595	chr2:178724275;178724274;178724273	chr2:179589002;179589001;179589000
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-54
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.223
• 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/E	rs1409920305	-1.264	0.042	N	0.489	0.259	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
V/E	rs1409920305	-1.264	0.042	N	0.489	0.259	None	gnomAD-4.0.0	1.59352E-06	None	None	None	None	N	None	5.67472E-05	0	None	0	0	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
V/A	0.0942	likely_benign	0.086	benign	-0.928	Destabilizing	0.019	N	0.355	neutral	N	0.455116049	None	None	N
V/C	0.6498	likely_pathogenic	0.6148	pathogenic	-0.804	Destabilizing	0.859	D	0.537	neutral	None	None	None	None	N
V/D	0.1602	likely_benign	0.1514	benign	-0.278	Destabilizing	0.22	N	0.552	neutral	None	None	None	None	N
V/E	0.14	likely_benign	0.1304	benign	-0.339	Destabilizing	0.042	N	0.489	neutral	N	0.416960305	None	None	N
V/F	0.1034	likely_benign	0.0931	benign	-0.89	Destabilizing	0.124	N	0.58	neutral	None	None	None	None	N
V/G	0.1462	likely_benign	0.1352	benign	-1.159	Destabilizing	0.042	N	0.519	neutral	D	0.530421884	None	None	N
V/H	0.2833	likely_benign	0.2541	benign	-0.699	Destabilizing	0.667	D	0.588	neutral	None	None	None	None	N
V/I	0.0752	likely_benign	0.073	benign	-0.438	Destabilizing	0.055	N	0.407	neutral	None	None	None	None	N
V/K	0.1424	likely_benign	0.1346	benign	-0.644	Destabilizing	0.002	N	0.327	neutral	None	None	None	None	N
V/L	0.1189	likely_benign	0.1044	benign	-0.438	Destabilizing	None	N	0.161	neutral	N	0.452230459	None	None	N
V/M	0.0855	likely_benign	0.0801	benign	-0.384	Destabilizing	0.003	N	0.357	neutral	N	0.471779012	None	None	N
V/N	0.1361	likely_benign	0.1256	benign	-0.375	Destabilizing	0.22	N	0.576	neutral	None	None	None	None	N
V/P	0.4407	ambiguous	0.4002	ambiguous	-0.564	Destabilizing	0.364	N	0.546	neutral	None	None	None	None	N
V/Q	0.1564	likely_benign	0.1435	benign	-0.579	Destabilizing	0.011	N	0.337	neutral	None	None	None	None	N
V/R	0.1296	likely_benign	0.1195	benign	-0.182	Destabilizing	0.124	N	0.556	neutral	None	None	None	None	N
V/S	0.1056	likely_benign	0.0959	benign	-0.911	Destabilizing	0.002	N	0.327	neutral	None	None	None	None	N
V/T	0.0954	likely_benign	0.0894	benign	-0.858	Destabilizing	0.001	N	0.152	neutral	None	None	None	None	N
V/W	0.5561	ambiguous	0.4854	ambiguous	-0.977	Destabilizing	0.958	D	0.594	neutral	None	None	None	None	N
V/Y	0.3663	ambiguous	0.3232	benign	-0.671	Destabilizing	0.667	D	0.569	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.