TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16879	50860;50861;50862	chr2:178611594;178611593;178611592	chr2:179476321;179476320;179476319
N2AB	15238	45937;45938;45939	chr2:178611594;178611593;178611592	chr2:179476321;179476320;179476319
N2A	14311	43156;43157;43158	chr2:178611594;178611593;178611592	chr2:179476321;179476320;179476319
N2B	7814	23665;23666;23667	chr2:178611594;178611593;178611592	chr2:179476321;179476320;179476319
Novex-1	7939	24040;24041;24042	chr2:178611594;178611593;178611592	chr2:179476321;179476320;179476319
Novex-2	8006	24241;24242;24243	chr2:178611594;178611593;178611592	chr2:179476321;179476320;179476319
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-11
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2998
• 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
N/S	rs961819601	-0.586	0.055	N	0.481	0.135	0.16115917748	gnomAD-2.1.1	8.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
N/S	rs961819601	-0.586	0.055	N	0.481	0.135	0.16115917748	gnomAD-4.0.0	7.96511E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.43073E-05	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
N/A	0.6192	likely_pathogenic	0.7566	pathogenic	-0.726	Destabilizing	0.272	N	0.595	neutral	None	None	None	None	I
N/C	0.7601	likely_pathogenic	0.8624	pathogenic	0.125	Stabilizing	0.968	D	0.709	prob.delet.	None	None	None	None	I
N/D	0.1224	likely_benign	0.1362	benign	-0.547	Destabilizing	None	N	0.104	neutral	N	0.404019171	None	None	I
N/E	0.7799	likely_pathogenic	0.8826	pathogenic	-0.512	Destabilizing	0.072	N	0.45	neutral	None	None	None	None	I
N/F	0.9148	likely_pathogenic	0.9598	pathogenic	-0.822	Destabilizing	0.89	D	0.695	prob.neutral	None	None	None	None	I
N/G	0.6307	likely_pathogenic	0.7277	pathogenic	-0.995	Destabilizing	0.133	N	0.455	neutral	None	None	None	None	I
N/H	0.4671	ambiguous	0.5866	pathogenic	-0.993	Destabilizing	0.667	D	0.587	neutral	D	0.540047154	None	None	I
N/I	0.7371	likely_pathogenic	0.8591	pathogenic	-0.073	Destabilizing	0.667	D	0.703	prob.neutral	N	0.481419669	None	None	I
N/K	0.8599	likely_pathogenic	0.9356	pathogenic	-0.128	Destabilizing	0.22	N	0.46	neutral	N	0.517258583	None	None	I
N/L	0.6987	likely_pathogenic	0.841	pathogenic	-0.073	Destabilizing	0.726	D	0.64	neutral	None	None	None	None	I
N/M	0.7656	likely_pathogenic	0.8684	pathogenic	0.543	Stabilizing	0.968	D	0.679	prob.neutral	None	None	None	None	I
N/P	0.8422	likely_pathogenic	0.9099	pathogenic	-0.262	Destabilizing	0.726	D	0.667	neutral	None	None	None	None	I
N/Q	0.8134	likely_pathogenic	0.9018	pathogenic	-0.806	Destabilizing	0.567	D	0.529	neutral	None	None	None	None	I
N/R	0.8849	likely_pathogenic	0.9488	pathogenic	-0.099	Destabilizing	0.567	D	0.527	neutral	None	None	None	None	I
N/S	0.1784	likely_benign	0.217	benign	-0.609	Destabilizing	0.055	N	0.481	neutral	N	0.470099282	None	None	I
N/T	0.3291	likely_benign	0.4075	ambiguous	-0.4	Destabilizing	0.22	N	0.447	neutral	N	0.477127158	None	None	I
N/V	0.7289	likely_pathogenic	0.8463	pathogenic	-0.262	Destabilizing	0.726	D	0.673	neutral	None	None	None	None	I
N/W	0.9676	likely_pathogenic	0.986	pathogenic	-0.638	Destabilizing	0.968	D	0.725	prob.delet.	None	None	None	None	I
N/Y	0.5312	ambiguous	0.7105	pathogenic	-0.405	Destabilizing	0.859	D	0.687	prob.neutral	D	0.635097274	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.