TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16112	48559;48560;48561	chr2:178615767;178615766;178615765	chr2:179480494;179480493;179480492
N2AB	14471	43636;43637;43638	chr2:178615767;178615766;178615765	chr2:179480494;179480493;179480492
N2A	13544	40855;40856;40857	chr2:178615767;178615766;178615765	chr2:179480494;179480493;179480492
N2B	7047	21364;21365;21366	chr2:178615767;178615766;178615765	chr2:179480494;179480493;179480492
Novex-1	7172	21739;21740;21741	chr2:178615767;178615766;178615765	chr2:179480494;179480493;179480492
Novex-2	7239	21940;21941;21942	chr2:178615767;178615766;178615765	chr2:179480494;179480493;179480492
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-4
• Domain position: 58
• Structural Position: 89
• Q(SASA): 0.2694
• 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
L/V	rs747917712	-1.045	0.722	N	0.465	0.185	0.396794106654	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
L/V	rs747917712	-1.045	0.722	N	0.465	0.185	0.396794106654	gnomAD-4.0.0	3.42527E-06	None	None	None	None	N	None	2.99796E-05	0	None	0	0	None	0	0	2.70086E-06	0	1.6597E-05

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
L/A	0.1902	likely_benign	0.2376	benign	-1.893	Destabilizing	0.633	D	0.517	neutral	None	None	None	None	N
L/C	0.3746	ambiguous	0.4679	ambiguous	-1.051	Destabilizing	0.996	D	0.646	neutral	None	None	None	None	N
L/D	0.6009	likely_pathogenic	0.6758	pathogenic	-1.736	Destabilizing	0.923	D	0.669	neutral	None	None	None	None	N
L/E	0.2617	likely_benign	0.3054	benign	-1.586	Destabilizing	0.633	D	0.611	neutral	None	None	None	None	N
L/F	0.2094	likely_benign	0.2706	benign	-1.124	Destabilizing	0.987	D	0.53	neutral	None	None	None	None	N
L/G	0.3738	ambiguous	0.4422	ambiguous	-2.34	Highly Destabilizing	0.923	D	0.668	neutral	None	None	None	None	N
L/H	0.2408	likely_benign	0.3099	benign	-1.553	Destabilizing	0.979	D	0.729	prob.delet.	None	None	None	None	N
L/I	0.1359	likely_benign	0.1539	benign	-0.656	Destabilizing	0.84	D	0.422	neutral	N	0.475417481	None	None	N
L/K	0.182	likely_benign	0.2235	benign	-1.311	Destabilizing	0.633	D	0.565	neutral	None	None	None	None	N
L/M	0.0945	likely_benign	0.1105	benign	-0.534	Destabilizing	0.961	D	0.569	neutral	None	None	None	None	N
L/N	0.2534	likely_benign	0.2848	benign	-1.469	Destabilizing	0.923	D	0.69	prob.neutral	None	None	None	None	N
L/P	0.1991	likely_benign	0.2509	benign	-1.043	Destabilizing	0.949	D	0.714	prob.delet.	N	0.473030558	None	None	N
L/Q	0.1116	likely_benign	0.1427	benign	-1.447	Destabilizing	0.014	N	0.443	neutral	N	0.462583315	None	None	N
L/R	0.1546	likely_benign	0.2071	benign	-0.924	Destabilizing	0.82	D	0.641	neutral	N	0.473563836	None	None	N
L/S	0.2072	likely_benign	0.2531	benign	-2.122	Highly Destabilizing	0.633	D	0.595	neutral	None	None	None	None	N
L/T	0.1186	likely_benign	0.1479	benign	-1.835	Destabilizing	0.775	D	0.537	neutral	None	None	None	None	N
L/V	0.1083	likely_benign	0.1304	benign	-1.043	Destabilizing	0.722	D	0.465	neutral	N	0.474938599	None	None	N
L/W	0.3247	likely_benign	0.4195	ambiguous	-1.38	Destabilizing	0.996	D	0.704	prob.neutral	None	None	None	None	N
L/Y	0.4009	ambiguous	0.5009	ambiguous	-1.059	Destabilizing	0.961	D	0.642	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.