TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23871	71836;71837;71838	chr2:178574521;178574520;178574519	chr2:179439248;179439247;179439246
N2AB	22230	66913;66914;66915	chr2:178574521;178574520;178574519	chr2:179439248;179439247;179439246
N2A	21303	64132;64133;64134	chr2:178574521;178574520;178574519	chr2:179439248;179439247;179439246
N2B	14806	44641;44642;44643	chr2:178574521;178574520;178574519	chr2:179439248;179439247;179439246
Novex-1	14931	45016;45017;45018	chr2:178574521;178574520;178574519	chr2:179439248;179439247;179439246
Novex-2	14998	45217;45218;45219	chr2:178574521;178574520;178574519	chr2:179439248;179439247;179439246
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-61
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.7442
• 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/T	rs770250820	-0.553	1.0	N	0.503	0.414	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
I/T	rs770250820	-0.553	1.0	N	0.503	0.414	None	gnomAD-4.0.0	1.59163E-06	None	None	None	None	N	None	0	0	None	0	2.77393E-05	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
I/A	0.8568	likely_pathogenic	0.7964	pathogenic	-0.533	Destabilizing	0.999	D	0.509	neutral	None	None	None	None	N
I/C	0.9223	likely_pathogenic	0.8781	pathogenic	-0.903	Destabilizing	1.0	D	0.578	neutral	None	None	None	None	N
I/D	0.9603	likely_pathogenic	0.9443	pathogenic	-0.246	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
I/E	0.9511	likely_pathogenic	0.9348	pathogenic	-0.324	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
I/F	0.364	ambiguous	0.2839	benign	-0.688	Destabilizing	1.0	D	0.559	neutral	N	0.490447318	None	None	N
I/G	0.9465	likely_pathogenic	0.919	pathogenic	-0.617	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
I/H	0.8796	likely_pathogenic	0.8223	pathogenic	0.06	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
I/K	0.8728	likely_pathogenic	0.8274	pathogenic	-0.408	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
I/L	0.1695	likely_benign	0.1412	benign	-0.417	Destabilizing	0.993	D	0.357	neutral	N	0.441250169	None	None	N
I/M	0.2325	likely_benign	0.1815	benign	-0.764	Destabilizing	1.0	D	0.569	neutral	N	0.494391221	None	None	N
I/N	0.7176	likely_pathogenic	0.644	pathogenic	-0.317	Destabilizing	1.0	D	0.63	neutral	N	0.474706595	None	None	N
I/P	0.8967	likely_pathogenic	0.8667	pathogenic	-0.432	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
I/Q	0.883	likely_pathogenic	0.8413	pathogenic	-0.457	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
I/R	0.8205	likely_pathogenic	0.7624	pathogenic	0.015	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
I/S	0.7772	likely_pathogenic	0.708	pathogenic	-0.701	Destabilizing	1.0	D	0.548	neutral	N	0.469647492	None	None	N
I/T	0.8434	likely_pathogenic	0.7912	pathogenic	-0.684	Destabilizing	1.0	D	0.503	neutral	N	0.483654152	None	None	N
I/V	0.2407	likely_benign	0.1926	benign	-0.432	Destabilizing	0.993	D	0.365	neutral	N	0.495930016	None	None	N
I/W	0.902	likely_pathogenic	0.8626	pathogenic	-0.693	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
I/Y	0.7067	likely_pathogenic	0.643	pathogenic	-0.487	Destabilizing	1.0	D	0.559	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.