TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9401	28426;28427;28428	chr2:178710896;178710895;178710894	chr2:179575623;179575622;179575621
N2AB	9084	27475;27476;27477	chr2:178710896;178710895;178710894	chr2:179575623;179575622;179575621
N2A	8157	24694;24695;24696	chr2:178710896;178710895;178710894	chr2:179575623;179575622;179575621
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-80
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.418
• Predicted PPI site: I

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	0.772	None	0.281	0.311	0.463586170655	gnomAD-4.0.0	1.59235E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41546E-04	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
I/A	0.2948	likely_benign	0.3077	benign	-1.271	Destabilizing	0.103	N	0.268	neutral	None	None	None	None	I
I/C	0.672	likely_pathogenic	0.668	pathogenic	-0.442	Destabilizing	0.991	D	0.311	neutral	None	None	None	None	I
I/D	0.5124	ambiguous	0.5263	ambiguous	-0.967	Destabilizing	0.561	D	0.346	neutral	None	None	None	None	I
I/E	0.3552	ambiguous	0.3498	ambiguous	-1.035	Destabilizing	0.209	N	0.301	neutral	None	None	None	None	I
I/F	0.1588	likely_benign	0.1644	benign	-1.1	Destabilizing	0.772	D	0.281	neutral	None	None	None	None	I
I/G	0.541	ambiguous	0.567	pathogenic	-1.518	Destabilizing	0.561	D	0.327	neutral	None	None	None	None	I
I/H	0.3263	likely_benign	0.3443	ambiguous	-0.808	Destabilizing	0.901	D	0.323	neutral	None	None	None	None	I
I/K	0.1792	likely_benign	0.18	benign	-0.76	Destabilizing	0.017	N	0.239	neutral	None	None	None	None	I
I/L	0.1227	likely_benign	0.1273	benign	-0.697	Destabilizing	0.08	N	0.142	neutral	None	None	None	None	I
I/M	0.1078	likely_benign	0.1124	benign	-0.331	Destabilizing	0.873	D	0.288	neutral	None	None	None	None	I
I/N	0.1713	likely_benign	0.1845	benign	-0.387	Destabilizing	0.491	N	0.355	neutral	None	None	None	None	I
I/P	0.8245	likely_pathogenic	0.8089	pathogenic	-0.856	Destabilizing	0.722	D	0.368	neutral	None	None	None	None	I
I/Q	0.2555	likely_benign	0.2664	benign	-0.668	Destabilizing	0.047	N	0.273	neutral	None	None	None	None	I
I/R	0.1424	likely_benign	0.1455	benign	-0.086	Destabilizing	0.004	N	0.243	neutral	None	None	None	None	I
I/S	0.2103	likely_benign	0.2201	benign	-0.856	Destabilizing	0.166	N	0.275	neutral	None	None	None	None	I
I/T	0.1883	likely_benign	0.1825	benign	-0.823	Destabilizing	0.005	N	0.114	neutral	None	None	None	None	I
I/V	0.094	likely_benign	0.0893	benign	-0.856	Destabilizing	0.001	N	0.132	neutral	None	None	None	None	I
I/W	0.7281	likely_pathogenic	0.7409	pathogenic	-1.141	Destabilizing	0.991	D	0.321	neutral	None	None	None	None	I
I/Y	0.3697	ambiguous	0.3851	ambiguous	-0.929	Destabilizing	0.901	D	0.365	neutral	None	None	None	None	I

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.