TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8833	26722;26723;26724	chr2:178714161;178714160;178714159	chr2:179578888;179578887;179578886
N2AB	8516	25771;25772;25773	chr2:178714161;178714160;178714159	chr2:179578888;179578887;179578886
N2A	7589	22990;22991;22992	chr2:178714161;178714160;178714159	chr2:179578888;179578887;179578886
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-74
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.6133
• 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/L	rs1316360664	-0.213	0.001	N	0.069	0.09	0.141422826196	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.39E-05	None	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	0.1178	likely_benign	0.132	benign	-0.775	Destabilizing	0.505	D	0.398	neutral	N	0.460376149	None	None	N
V/C	0.6753	likely_pathogenic	0.7296	pathogenic	-0.709	Destabilizing	0.991	D	0.48	neutral	None	None	None	None	N
V/D	0.2984	likely_benign	0.3372	benign	-0.567	Destabilizing	0.967	D	0.569	neutral	None	None	None	None	N
V/E	0.1847	likely_benign	0.2162	benign	-0.668	Destabilizing	0.879	D	0.566	neutral	N	0.50771473	None	None	N
V/F	0.1395	likely_benign	0.1501	benign	-0.843	Destabilizing	0.01	N	0.225	neutral	None	None	None	None	N
V/G	0.1803	likely_benign	0.2078	benign	-0.947	Destabilizing	0.879	D	0.55	neutral	N	0.479747851	None	None	N
V/H	0.4155	ambiguous	0.4598	ambiguous	-0.431	Destabilizing	0.991	D	0.583	neutral	None	None	None	None	N
V/I	0.0671	likely_benign	0.0668	benign	-0.462	Destabilizing	0.003	N	0.149	neutral	N	0.425520208	None	None	N
V/K	0.2034	likely_benign	0.2346	benign	-0.708	Destabilizing	0.906	D	0.558	neutral	None	None	None	None	N
V/L	0.1092	likely_benign	0.1105	benign	-0.462	Destabilizing	0.001	N	0.069	neutral	N	0.447068916	None	None	N
V/M	0.0938	likely_benign	0.1086	benign	-0.402	Destabilizing	0.826	D	0.437	neutral	None	None	None	None	N
V/N	0.2334	likely_benign	0.2647	benign	-0.451	Destabilizing	0.967	D	0.577	neutral	None	None	None	None	N
V/P	0.6436	likely_pathogenic	0.6464	pathogenic	-0.531	Destabilizing	0.967	D	0.547	neutral	None	None	None	None	N
V/Q	0.2028	likely_benign	0.232	benign	-0.714	Destabilizing	0.967	D	0.549	neutral	None	None	None	None	N
V/R	0.1611	likely_benign	0.1824	benign	-0.107	Destabilizing	0.906	D	0.577	neutral	None	None	None	None	N
V/S	0.1527	likely_benign	0.1732	benign	-0.841	Destabilizing	0.906	D	0.493	neutral	None	None	None	None	N
V/T	0.0979	likely_benign	0.1103	benign	-0.842	Destabilizing	0.575	D	0.403	neutral	None	None	None	None	N
V/W	0.5898	likely_pathogenic	0.6498	pathogenic	-0.916	Destabilizing	0.991	D	0.624	neutral	None	None	None	None	N
V/Y	0.4372	ambiguous	0.4679	ambiguous	-0.642	Destabilizing	0.704	D	0.463	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.