TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32950	99073;99074;99075	chr2:178539087;178539086;178539085	chr2:179403814;179403813;179403812
N2AB	31309	94150;94151;94152	chr2:178539087;178539086;178539085	chr2:179403814;179403813;179403812
N2A	30382	91369;91370;91371	chr2:178539087;178539086;178539085	chr2:179403814;179403813;179403812
N2B	23885	71878;71879;71880	chr2:178539087;178539086;178539085	chr2:179403814;179403813;179403812
Novex-1	24010	72253;72254;72255	chr2:178539087;178539086;178539085	chr2:179403814;179403813;179403812
Novex-2	24077	72454;72455;72456	chr2:178539087;178539086;178539085	chr2:179403814;179403813;179403812
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-128
• Domain position: 55
• Structural Position: 72
• Q(SASA): 0.6381
• 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
T/I	None	None	1.0	N	0.659	0.434	0.451786746415	gnomAD-4.0.0	1.59131E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
T/A	0.1698	likely_benign	0.1998	benign	-0.272	Destabilizing	0.999	D	0.501	neutral	N	0.488542684	None	None	I
T/C	0.7306	likely_pathogenic	0.7694	pathogenic	-0.346	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
T/D	0.7101	likely_pathogenic	0.761	pathogenic	0.327	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	I
T/E	0.5981	likely_pathogenic	0.6555	pathogenic	0.273	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
T/F	0.5179	ambiguous	0.5818	pathogenic	-0.729	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
T/G	0.4712	ambiguous	0.5346	ambiguous	-0.412	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
T/H	0.4773	ambiguous	0.5437	ambiguous	-0.549	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	I
T/I	0.3463	ambiguous	0.3865	ambiguous	-0.021	Destabilizing	1.0	D	0.659	neutral	N	0.491545704	None	None	I
T/K	0.5367	ambiguous	0.5685	pathogenic	-0.279	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
T/L	0.2201	likely_benign	0.2569	benign	-0.021	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
T/M	0.1502	likely_benign	0.1649	benign	-0.129	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
T/N	0.21	likely_benign	0.2439	benign	-0.14	Destabilizing	1.0	D	0.671	neutral	N	0.504320213	None	None	I
T/P	0.6097	likely_pathogenic	0.6771	pathogenic	-0.075	Destabilizing	1.0	D	0.645	neutral	N	0.484787516	None	None	I
T/Q	0.3947	ambiguous	0.4504	ambiguous	-0.286	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
T/R	0.4975	ambiguous	0.5276	ambiguous	-0.014	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
T/S	0.2081	likely_benign	0.2493	benign	-0.361	Destabilizing	0.999	D	0.517	neutral	N	0.458449063	None	None	I
T/V	0.244	likely_benign	0.2818	benign	-0.075	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	I
T/W	0.8612	likely_pathogenic	0.8899	pathogenic	-0.782	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
T/Y	0.5567	ambiguous	0.6143	pathogenic	-0.473	Destabilizing	1.0	D	0.682	prob.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.