TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34350	103273;103274;103275	chr2:178533567;178533566;178533565	chr2:179398294;179398293;179398292
N2AB	32709	98350;98351;98352	chr2:178533567;178533566;178533565	chr2:179398294;179398293;179398292
N2A	31782	95569;95570;95571	chr2:178533567;178533566;178533565	chr2:179398294;179398293;179398292
N2B	25285	76078;76079;76080	chr2:178533567;178533566;178533565	chr2:179398294;179398293;179398292
Novex-1	25410	76453;76454;76455	chr2:178533567;178533566;178533565	chr2:179398294;179398293;179398292
Novex-2	25477	76654;76655;76656	chr2:178533567;178533566;178533565	chr2:179398294;179398293;179398292
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-161
• Domain position: 93
• Structural Position: 178
• Q(SASA): 0.3331
• 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	None	None	0.09	N	0.701	0.325	0.37097340754	gnomAD-4.0.0	4.77319E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57305E-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	0.8782	likely_pathogenic	0.8727	pathogenic	-1.546	Destabilizing	0.581	D	0.673	neutral	D	0.527904184	None	None	N
V/C	0.9799	likely_pathogenic	0.9787	pathogenic	-1.4	Destabilizing	0.993	D	0.803	deleterious	None	None	None	None	N
V/D	0.9977	likely_pathogenic	0.9982	pathogenic	-1.846	Destabilizing	0.929	D	0.804	deleterious	None	None	None	None	N
V/E	0.9918	likely_pathogenic	0.9932	pathogenic	-1.853	Destabilizing	0.908	D	0.794	deleterious	D	0.540185542	None	None	N
V/F	0.9339	likely_pathogenic	0.9445	pathogenic	-1.415	Destabilizing	0.866	D	0.809	deleterious	None	None	None	None	N
V/G	0.9608	likely_pathogenic	0.9641	pathogenic	-1.833	Destabilizing	0.908	D	0.775	deleterious	D	0.540185542	None	None	N
V/H	0.9981	likely_pathogenic	0.9983	pathogenic	-1.326	Destabilizing	0.993	D	0.781	deleterious	None	None	None	None	N
V/I	0.1174	likely_benign	0.1125	benign	-0.852	Destabilizing	0.004	N	0.556	neutral	N	0.504186927	None	None	N
V/K	0.9911	likely_pathogenic	0.9925	pathogenic	-1.179	Destabilizing	0.929	D	0.795	deleterious	None	None	None	None	N
V/L	0.7806	likely_pathogenic	0.8	pathogenic	-0.852	Destabilizing	0.09	N	0.701	prob.neutral	N	0.515280431	None	None	N
V/M	0.7919	likely_pathogenic	0.8015	pathogenic	-0.755	Destabilizing	0.866	D	0.822	deleterious	None	None	None	None	N
V/N	0.9892	likely_pathogenic	0.991	pathogenic	-1.093	Destabilizing	0.976	D	0.814	deleterious	None	None	None	None	N
V/P	0.98	likely_pathogenic	0.9832	pathogenic	-1.052	Destabilizing	0.976	D	0.811	deleterious	None	None	None	None	N
V/Q	0.9922	likely_pathogenic	0.9929	pathogenic	-1.338	Destabilizing	0.976	D	0.823	deleterious	None	None	None	None	N
V/R	0.9863	likely_pathogenic	0.9879	pathogenic	-0.673	Destabilizing	0.929	D	0.813	deleterious	None	None	None	None	N
V/S	0.9658	likely_pathogenic	0.9673	pathogenic	-1.595	Destabilizing	0.929	D	0.772	deleterious	None	None	None	None	N
V/T	0.8861	likely_pathogenic	0.8855	pathogenic	-1.499	Destabilizing	0.648	D	0.746	deleterious	None	None	None	None	N
V/W	0.9993	likely_pathogenic	0.9993	pathogenic	-1.563	Destabilizing	0.993	D	0.762	deleterious	None	None	None	None	N
V/Y	0.9956	likely_pathogenic	0.9959	pathogenic	-1.242	Destabilizing	0.929	D	0.816	deleterious	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.