TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18092	54499;54500;54501	chr2:178604815;178604814;178604813	chr2:179469542;179469541;179469540
N2AB	16451	49576;49577;49578	chr2:178604815;178604814;178604813	chr2:179469542;179469541;179469540
N2A	15524	46795;46796;46797	chr2:178604815;178604814;178604813	chr2:179469542;179469541;179469540
N2B	9027	27304;27305;27306	chr2:178604815;178604814;178604813	chr2:179469542;179469541;179469540
Novex-1	9152	27679;27680;27681	chr2:178604815;178604814;178604813	chr2:179469542;179469541;179469540
Novex-2	9219	27880;27881;27882	chr2:178604815;178604814;178604813	chr2:179469542;179469541;179469540
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: Fn3-19
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.4201
• 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
N/D	None	None	0.031	N	0.128	0.13	0.195762928549	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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	0.5246	ambiguous	0.4952	ambiguous	-0.591	Destabilizing	0.97	D	0.645	neutral	None	None	None	None	N
N/C	0.6216	likely_pathogenic	0.6009	pathogenic	0.139	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
N/D	0.0969	likely_benign	0.088	benign	-1.006	Destabilizing	0.031	N	0.128	neutral	N	0.422181619	None	None	N
N/E	0.7585	likely_pathogenic	0.7415	pathogenic	-0.993	Destabilizing	0.942	D	0.546	neutral	None	None	None	None	N
N/F	0.8703	likely_pathogenic	0.8419	pathogenic	-0.928	Destabilizing	0.996	D	0.726	prob.delet.	None	None	None	None	N
N/G	0.5594	ambiguous	0.5443	ambiguous	-0.818	Destabilizing	0.985	D	0.535	neutral	None	None	None	None	N
N/H	0.3822	ambiguous	0.3415	ambiguous	-0.946	Destabilizing	0.998	D	0.597	neutral	N	0.51026475	None	None	N
N/I	0.6518	likely_pathogenic	0.5797	pathogenic	-0.06	Destabilizing	0.433	N	0.527	neutral	N	0.520039027	None	None	N
N/K	0.8322	likely_pathogenic	0.7955	pathogenic	-0.075	Destabilizing	0.98	D	0.557	neutral	N	0.468442269	None	None	N
N/L	0.611	likely_pathogenic	0.5579	ambiguous	-0.06	Destabilizing	0.942	D	0.689	prob.neutral	None	None	None	None	N
N/M	0.7176	likely_pathogenic	0.6699	pathogenic	0.662	Stabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
N/P	0.854	likely_pathogenic	0.864	pathogenic	-0.21	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
N/Q	0.7791	likely_pathogenic	0.753	pathogenic	-0.91	Destabilizing	0.996	D	0.576	neutral	None	None	None	None	N
N/R	0.8293	likely_pathogenic	0.7838	pathogenic	0.053	Stabilizing	0.996	D	0.584	neutral	None	None	None	None	N
N/S	0.118	likely_benign	0.1134	benign	-0.523	Destabilizing	0.961	D	0.553	neutral	N	0.498391531	None	None	N
N/T	0.197	likely_benign	0.1791	benign	-0.357	Destabilizing	0.98	D	0.565	neutral	N	0.503682708	None	None	N
N/V	0.6016	likely_pathogenic	0.545	ambiguous	-0.21	Destabilizing	0.942	D	0.69	prob.neutral	None	None	None	None	N
N/W	0.9635	likely_pathogenic	0.9557	pathogenic	-0.819	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
N/Y	0.5478	ambiguous	0.4879	ambiguous	-0.523	Destabilizing	0.998	D	0.714	prob.delet.	N	0.49532239	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.