TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35685	107278;107279;107280	chr2:178528698;178528697;178528696	chr2:179393425;179393424;179393423
N2AB	34044	102355;102356;102357	chr2:178528698;178528697;178528696	chr2:179393425;179393424;179393423
N2A	33117	99574;99575;99576	chr2:178528698;178528697;178528696	chr2:179393425;179393424;179393423
N2B	26620	80083;80084;80085	chr2:178528698;178528697;178528696	chr2:179393425;179393424;179393423
Novex-1	26745	80458;80459;80460	chr2:178528698;178528697;178528696	chr2:179393425;179393424;179393423
Novex-2	26812	80659;80660;80661	chr2:178528698;178528697;178528696	chr2:179393425;179393424;179393423
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-167
• Domain position: 79
• Structural Position: 165
• Q(SASA): 0.4046
• 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
I/F	None	None	0.171	N	0.364	0.078	0.416581338634	gnomAD-4.0.0	1.59179E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43398E-05	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
I/A	0.2669	likely_benign	0.2631	benign	-1.551	Destabilizing	0.016	N	0.429	neutral	None	None	None	None	N
I/C	0.8233	likely_pathogenic	0.7951	pathogenic	-0.945	Destabilizing	0.676	D	0.493	neutral	None	None	None	None	N
I/D	0.5275	ambiguous	0.5326	ambiguous	-0.712	Destabilizing	0.214	N	0.597	neutral	None	None	None	None	N
I/E	0.4393	ambiguous	0.4356	ambiguous	-0.723	Destabilizing	0.072	N	0.613	neutral	None	None	None	None	N
I/F	0.1754	likely_benign	0.1712	benign	-1.078	Destabilizing	0.171	N	0.364	neutral	N	0.460119224	None	None	N
I/G	0.6666	likely_pathogenic	0.6442	pathogenic	-1.861	Destabilizing	0.072	N	0.606	neutral	None	None	None	None	N
I/H	0.5068	ambiguous	0.5072	ambiguous	-1.033	Destabilizing	0.864	D	0.579	neutral	None	None	None	None	N
I/K	0.3547	ambiguous	0.363	ambiguous	-0.976	Destabilizing	0.001	N	0.431	neutral	None	None	None	None	N
I/L	0.1349	likely_benign	0.1342	benign	-0.787	Destabilizing	None	N	0.138	neutral	N	0.441186746	None	None	N
I/M	0.1153	likely_benign	0.1122	benign	-0.619	Destabilizing	0.344	N	0.399	neutral	N	0.460119224	None	None	N
I/N	0.2158	likely_benign	0.22	benign	-0.725	Destabilizing	0.171	N	0.595	neutral	N	0.459252432	None	None	N
I/P	0.7196	likely_pathogenic	0.6902	pathogenic	-1.01	Destabilizing	0.356	N	0.596	neutral	None	None	None	None	N
I/Q	0.4508	ambiguous	0.4419	ambiguous	-0.913	Destabilizing	0.214	N	0.603	neutral	None	None	None	None	N
I/R	0.2663	likely_benign	0.2721	benign	-0.401	Destabilizing	0.12	N	0.599	neutral	None	None	None	None	N
I/S	0.2439	likely_benign	0.2446	benign	-1.381	Destabilizing	0.029	N	0.552	neutral	N	0.457692207	None	None	N
I/T	0.1388	likely_benign	0.1374	benign	-1.274	Destabilizing	0.001	N	0.285	neutral	N	0.440146596	None	None	N
I/V	0.0918	likely_benign	0.0853	benign	-1.01	Destabilizing	None	N	0.162	neutral	N	0.429969675	None	None	N
I/W	0.7581	likely_pathogenic	0.7496	pathogenic	-1.094	Destabilizing	0.864	D	0.597	neutral	None	None	None	None	N
I/Y	0.47	ambiguous	0.4608	ambiguous	-0.889	Destabilizing	0.356	N	0.502	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.