TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7711	23356;23357;23358	chr2:178720631;178720630;178720629	chr2:179585358;179585357;179585356
N2AB	7394	22405;22406;22407	chr2:178720631;178720630;178720629	chr2:179585358;179585357;179585356
N2A	6467	19624;19625;19626	chr2:178720631;178720630;178720629	chr2:179585358;179585357;179585356
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-62
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3041
• 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	0.003	N	0.225	0.242	0.417843521124	gnomAD-4.0.0	1.60995E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88123E-06	0	0
V/L	rs771533917	-0.173	None	N	0.103	0.155	0.107399877778	gnomAD-2.1.1	1.67E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.66E-05	0
V/L	rs771533917	-0.173	None	N	0.103	0.155	0.107399877778	gnomAD-4.0.0	3.4435E-06	None	None	None	None	N	None	3.04173E-05	0	None	0	0	None	0	0	3.61013E-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	0.1108	likely_benign	0.1124	benign	-0.924	Destabilizing	0.003	N	0.225	neutral	N	0.50252878	None	None	N
V/C	0.6842	likely_pathogenic	0.6909	pathogenic	-0.793	Destabilizing	0.961	D	0.424	neutral	None	None	None	None	N
V/D	0.3887	ambiguous	0.4222	ambiguous	-0.341	Destabilizing	0.841	D	0.555	neutral	None	None	None	None	N
V/E	0.2605	likely_benign	0.286	benign	-0.377	Destabilizing	0.392	N	0.481	neutral	N	0.508301078	None	None	N
V/F	0.1302	likely_benign	0.1352	benign	-0.742	Destabilizing	0.496	N	0.402	neutral	None	None	None	None	N
V/G	0.2203	likely_benign	0.2296	benign	-1.187	Destabilizing	0.727	D	0.471	neutral	N	0.513314281	None	None	N
V/H	0.4766	ambiguous	0.5011	ambiguous	-0.77	Destabilizing	0.97	D	0.568	neutral	None	None	None	None	N
V/I	0.0722	likely_benign	0.0725	benign	-0.336	Destabilizing	None	N	0.114	neutral	N	0.505337012	None	None	N
V/K	0.3028	likely_benign	0.3352	benign	-0.776	Destabilizing	0.651	D	0.482	neutral	None	None	None	None	N
V/L	0.1386	likely_benign	0.1479	benign	-0.336	Destabilizing	None	N	0.103	neutral	N	0.502835425	None	None	N
V/M	0.1142	likely_benign	0.1199	benign	-0.375	Destabilizing	0.584	D	0.392	neutral	None	None	None	None	N
V/N	0.2746	likely_benign	0.2944	benign	-0.536	Destabilizing	0.458	N	0.563	neutral	None	None	None	None	N
V/P	0.6421	likely_pathogenic	0.6744	pathogenic	-0.495	Destabilizing	0.458	N	0.513	neutral	None	None	None	None	N
V/Q	0.2604	likely_benign	0.2783	benign	-0.681	Destabilizing	0.801	D	0.527	neutral	None	None	None	None	N
V/R	0.2671	likely_benign	0.2931	benign	-0.365	Destabilizing	0.799	D	0.558	neutral	None	None	None	None	N
V/S	0.1682	likely_benign	0.1713	benign	-1.057	Destabilizing	0.347	N	0.446	neutral	None	None	None	None	N
V/T	0.1213	likely_benign	0.1236	benign	-0.975	Destabilizing	0.109	N	0.353	neutral	None	None	None	None	N
V/W	0.7279	likely_pathogenic	0.7442	pathogenic	-0.888	Destabilizing	0.992	D	0.642	neutral	None	None	None	None	N
V/Y	0.4886	ambiguous	0.5032	ambiguous	-0.578	Destabilizing	0.799	D	0.425	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.