TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19555	58888;58889;58890	chr2:178593637;178593636;178593635	chr2:179458364;179458363;179458362
N2AB	17914	53965;53966;53967	chr2:178593637;178593636;178593635	chr2:179458364;179458363;179458362
N2A	16987	51184;51185;51186	chr2:178593637;178593636;178593635	chr2:179458364;179458363;179458362
N2B	10490	31693;31694;31695	chr2:178593637;178593636;178593635	chr2:179458364;179458363;179458362
Novex-1	10615	32068;32069;32070	chr2:178593637;178593636;178593635	chr2:179458364;179458363;179458362
Novex-2	10682	32269;32270;32271	chr2:178593637;178593636;178593635	chr2:179458364;179458363;179458362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-29
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.118
• 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
H/R	None	None	None	N	0.236	0.195	0.0716867268079	gnomAD-4.0.0	1.59301E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-05	0
H/Y	rs1289211242	0.178	None	N	0.158	0.144	0.0716867268079	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
H/Y	rs1289211242	0.178	None	N	0.158	0.144	0.0716867268079	gnomAD-4.0.0	6.84543E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9963E-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
H/A	0.3943	ambiguous	0.3796	ambiguous	-1.807	Destabilizing	0.015	N	0.663	neutral	None	None	None	None	N
H/C	0.1158	likely_benign	0.1098	benign	-1.053	Destabilizing	None	N	0.589	neutral	None	None	None	None	N
H/D	0.5913	likely_pathogenic	0.5462	ambiguous	-1.682	Destabilizing	0.111	N	0.709	prob.delet.	N	0.418874742	None	None	N
H/E	0.5719	likely_pathogenic	0.5483	ambiguous	-1.506	Destabilizing	0.033	N	0.531	neutral	None	None	None	None	N
H/F	0.1924	likely_benign	0.1626	benign	0.138	Stabilizing	0.033	N	0.68	prob.neutral	None	None	None	None	N
H/G	0.5199	ambiguous	0.4875	ambiguous	-2.195	Highly Destabilizing	0.064	N	0.708	prob.delet.	None	None	None	None	N
H/I	0.495	ambiguous	0.471	ambiguous	-0.66	Destabilizing	0.033	N	0.702	prob.neutral	None	None	None	None	N
H/K	0.4209	ambiguous	0.4063	ambiguous	-1.502	Destabilizing	0.033	N	0.681	prob.neutral	None	None	None	None	N
H/L	0.1883	likely_benign	0.178	benign	-0.66	Destabilizing	0.005	N	0.704	prob.neutral	N	0.356402131	None	None	N
H/M	0.4363	ambiguous	0.4284	ambiguous	-0.879	Destabilizing	0.003	N	0.492	neutral	None	None	None	None	N
H/N	0.2074	likely_benign	0.1927	benign	-1.897	Destabilizing	0.049	N	0.512	neutral	N	0.418874742	None	None	N
H/P	0.9392	likely_pathogenic	0.9306	pathogenic	-1.032	Destabilizing	0.202	N	0.717	prob.delet.	N	0.438153936	None	None	N
H/Q	0.2575	likely_benign	0.2315	benign	-1.459	Destabilizing	0.111	N	0.557	neutral	N	0.375523822	None	None	N
H/R	0.1776	likely_benign	0.1608	benign	-1.878	Destabilizing	None	N	0.236	neutral	N	0.302124929	None	None	N
H/S	0.2434	likely_benign	0.2228	benign	-1.991	Destabilizing	0.064	N	0.675	neutral	None	None	None	None	N
H/T	0.391	ambiguous	0.3583	ambiguous	-1.713	Destabilizing	0.064	N	0.705	prob.neutral	None	None	None	None	N
H/V	0.3784	ambiguous	0.3617	ambiguous	-1.032	Destabilizing	0.015	N	0.699	prob.neutral	None	None	None	None	N
H/W	0.3464	ambiguous	0.336	benign	0.574	Stabilizing	0.54	D	0.714	prob.delet.	None	None	None	None	N
H/Y	0.0812	likely_benign	0.0714	benign	0.384	Stabilizing	None	N	0.158	neutral	N	0.314920868	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.