TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14434	43525;43526;43527	chr2:178632706;178632705;178632704	chr2:179497433;179497432;179497431
N2AB	12793	38602;38603;38604	chr2:178632706;178632705;178632704	chr2:179497433;179497432;179497431
N2A	11866	35821;35822;35823	chr2:178632706;178632705;178632704	chr2:179497433;179497432;179497431
N2B	5369	16330;16331;16332	chr2:178632706;178632705;178632704	chr2:179497433;179497432;179497431
Novex-1	5494	16705;16706;16707	chr2:178632706;178632705;178632704	chr2:179497433;179497432;179497431
Novex-2	5561	16906;16907;16908	chr2:178632706;178632705;178632704	chr2:179497433;179497432;179497431
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-95
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.3466
• 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
E/D	None	None	0.896	N	0.389	0.332	0.355658859761	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	None	None	0.811	D	0.408	0.464	0.382592752248	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	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
E/A	0.1587	likely_benign	0.1489	benign	-0.462	Destabilizing	0.896	D	0.453	neutral	D	0.542337769	None	None	N
E/C	0.8984	likely_pathogenic	0.8832	pathogenic	-0.218	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
E/D	0.1972	likely_benign	0.2009	benign	-0.617	Destabilizing	0.896	D	0.389	neutral	N	0.520879236	None	None	N
E/F	0.748	likely_pathogenic	0.7367	pathogenic	-0.114	Destabilizing	0.976	D	0.64	neutral	None	None	None	None	N
E/G	0.2449	likely_benign	0.2436	benign	-0.731	Destabilizing	0.946	D	0.565	neutral	D	0.549316858	None	None	N
E/H	0.5932	likely_pathogenic	0.5763	pathogenic	-0.015	Destabilizing	0.997	D	0.401	neutral	None	None	None	None	N
E/I	0.2594	likely_benign	0.2378	benign	0.235	Stabilizing	0.952	D	0.621	neutral	None	None	None	None	N
E/K	0.1561	likely_benign	0.1597	benign	-0.004	Destabilizing	0.811	D	0.408	neutral	D	0.533298593	None	None	N
E/L	0.3315	likely_benign	0.3087	benign	0.235	Stabilizing	0.034	N	0.475	neutral	None	None	None	None	N
E/M	0.4009	ambiguous	0.3648	ambiguous	0.345	Stabilizing	0.993	D	0.606	neutral	None	None	None	None	N
E/N	0.3405	ambiguous	0.3465	ambiguous	-0.411	Destabilizing	0.988	D	0.409	neutral	None	None	None	None	N
E/P	0.4019	ambiguous	0.3955	ambiguous	0.024	Stabilizing	0.034	N	0.29	neutral	None	None	None	None	N
E/Q	0.1565	likely_benign	0.1545	benign	-0.33	Destabilizing	0.437	N	0.193	neutral	D	0.541072631	None	None	N
E/R	0.3092	likely_benign	0.3129	benign	0.305	Stabilizing	0.976	D	0.406	neutral	None	None	None	None	N
E/S	0.2622	likely_benign	0.2557	benign	-0.605	Destabilizing	0.919	D	0.375	neutral	None	None	None	None	N
E/T	0.2396	likely_benign	0.2268	benign	-0.387	Destabilizing	0.959	D	0.486	neutral	None	None	None	None	N
E/V	0.1566	likely_benign	0.1456	benign	0.024	Stabilizing	0.811	D	0.589	neutral	D	0.548223345	None	None	N
E/W	0.9325	likely_pathogenic	0.9237	pathogenic	0.086	Stabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
E/Y	0.66	likely_pathogenic	0.6359	pathogenic	0.134	Stabilizing	0.996	D	0.617	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.