TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25356	76291;76292;76293	chr2:178570066;178570065;178570064	chr2:179434793;179434792;179434791
N2AB	23715	71368;71369;71370	chr2:178570066;178570065;178570064	chr2:179434793;179434792;179434791
N2A	22788	68587;68588;68589	chr2:178570066;178570065;178570064	chr2:179434793;179434792;179434791
N2B	16291	49096;49097;49098	chr2:178570066;178570065;178570064	chr2:179434793;179434792;179434791
Novex-1	16416	49471;49472;49473	chr2:178570066;178570065;178570064	chr2:179434793;179434792;179434791
Novex-2	16483	49672;49673;49674	chr2:178570066;178570065;178570064	chr2:179434793;179434792;179434791
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-72
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.5556
• 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
K/T	rs765495476	None	0.988	N	0.649	0.309	0.353336612579	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.9332	likely_pathogenic	0.9122	pathogenic	0.119	Stabilizing	0.968	D	0.555	neutral	None	None	None	None	I
K/C	0.9602	likely_pathogenic	0.9555	pathogenic	-0.127	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
K/D	0.9664	likely_pathogenic	0.9538	pathogenic	-0.156	Destabilizing	0.995	D	0.675	prob.neutral	None	None	None	None	I
K/E	0.9072	likely_pathogenic	0.8665	pathogenic	-0.152	Destabilizing	0.958	D	0.543	neutral	N	0.466300542	None	None	I
K/F	0.9905	likely_pathogenic	0.987	pathogenic	-0.134	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
K/G	0.8757	likely_pathogenic	0.8489	pathogenic	-0.043	Destabilizing	0.991	D	0.583	neutral	None	None	None	None	I
K/H	0.7281	likely_pathogenic	0.7009	pathogenic	-0.209	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
K/I	0.9585	likely_pathogenic	0.9435	pathogenic	0.468	Stabilizing	0.995	D	0.699	prob.neutral	None	None	None	None	I
K/L	0.9189	likely_pathogenic	0.8954	pathogenic	0.468	Stabilizing	0.991	D	0.583	neutral	None	None	None	None	I
K/M	0.926	likely_pathogenic	0.8997	pathogenic	0.013	Stabilizing	0.999	D	0.675	prob.neutral	N	0.472761136	None	None	I
K/N	0.953	likely_pathogenic	0.9343	pathogenic	0.345	Stabilizing	0.988	D	0.68	prob.neutral	N	0.463998497	None	None	I
K/P	0.89	likely_pathogenic	0.8607	pathogenic	0.377	Stabilizing	0.998	D	0.657	neutral	None	None	None	None	I
K/Q	0.5799	likely_pathogenic	0.517	ambiguous	0.219	Stabilizing	0.988	D	0.681	prob.neutral	N	0.468886796	None	None	I
K/R	0.0887	likely_benign	0.0888	benign	0.072	Stabilizing	0.142	N	0.325	neutral	N	0.476901538	None	None	I
K/S	0.923	likely_pathogenic	0.8995	pathogenic	0.007	Stabilizing	0.968	D	0.587	neutral	None	None	None	None	I
K/T	0.8653	likely_pathogenic	0.8208	pathogenic	0.134	Stabilizing	0.988	D	0.649	neutral	N	0.496564734	None	None	I
K/V	0.9399	likely_pathogenic	0.9188	pathogenic	0.377	Stabilizing	0.995	D	0.645	neutral	None	None	None	None	I
K/W	0.9654	likely_pathogenic	0.9611	pathogenic	-0.248	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
K/Y	0.9531	likely_pathogenic	0.943	pathogenic	0.103	Stabilizing	0.998	D	0.663	neutral	None	None	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.