TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17945	54058;54059;54060	chr2:178605462;178605461;178605460	chr2:179470189;179470188;179470187
N2AB	16304	49135;49136;49137	chr2:178605462;178605461;178605460	chr2:179470189;179470188;179470187
N2A	15377	46354;46355;46356	chr2:178605462;178605461;178605460	chr2:179470189;179470188;179470187
N2B	8880	26863;26864;26865	chr2:178605462;178605461;178605460	chr2:179470189;179470188;179470187
Novex-1	9005	27238;27239;27240	chr2:178605462;178605461;178605460	chr2:179470189;179470188;179470187
Novex-2	9072	27439;27440;27441	chr2:178605462;178605461;178605460	chr2:179470189;179470188;179470187
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-18
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.516
• 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
E/D	rs556413709	-0.411	0.996	N	0.606	0.135	0.240491677333	gnomAD-2.1.1	2.83E-05	None	None	None	None	I	None	0	0	None	0	3.93479E-04	None	0	None	0	0	0
E/D	rs556413709	-0.411	0.996	N	0.606	0.135	0.240491677333	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.94932E-04	None	0	0	0	0	0
E/D	rs556413709	-0.411	0.996	N	0.606	0.135	0.240491677333	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/D	rs556413709	-0.411	0.996	N	0.606	0.135	0.240491677333	gnomAD-4.0.0	4.34399E-06	None	None	None	None	I	None	0	0	None	0	1.56754E-04	None	0	0	0	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
E/A	0.1745	likely_benign	0.1683	benign	-0.621	Destabilizing	0.996	D	0.704	prob.neutral	N	0.479747055	None	None	I
E/C	0.8366	likely_pathogenic	0.8168	pathogenic	-0.176	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/D	0.1961	likely_benign	0.2073	benign	-0.623	Destabilizing	0.996	D	0.606	neutral	N	0.483056719	None	None	I
E/F	0.7069	likely_pathogenic	0.6922	pathogenic	-0.226	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
E/G	0.3558	ambiguous	0.3075	benign	-0.889	Destabilizing	0.999	D	0.754	deleterious	N	0.473010945	None	None	I
E/H	0.6316	likely_pathogenic	0.5855	pathogenic	-0.124	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
E/I	0.255	likely_benign	0.2524	benign	0.079	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
E/K	0.3231	likely_benign	0.2458	benign	0.172	Stabilizing	0.992	D	0.706	prob.neutral	N	0.465452393	None	None	I
E/L	0.3781	ambiguous	0.3515	ambiguous	0.079	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
E/M	0.4339	ambiguous	0.4071	ambiguous	0.31	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
E/N	0.3868	ambiguous	0.3659	ambiguous	-0.376	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
E/P	0.4213	ambiguous	0.4247	ambiguous	-0.133	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
E/Q	0.2219	likely_benign	0.1888	benign	-0.3	Destabilizing	0.957	D	0.327	neutral	N	0.472994441	None	None	I
E/R	0.4863	ambiguous	0.4069	ambiguous	0.435	Stabilizing	0.999	D	0.792	deleterious	None	None	None	None	I
E/S	0.2831	likely_benign	0.2602	benign	-0.55	Destabilizing	0.997	D	0.743	deleterious	None	None	None	None	I
E/T	0.2596	likely_benign	0.2383	benign	-0.317	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
E/V	0.1625	likely_benign	0.1609	benign	-0.133	Destabilizing	0.999	D	0.807	deleterious	N	0.456600837	None	None	I
E/W	0.9226	likely_pathogenic	0.9141	pathogenic	0.045	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
E/Y	0.6698	likely_pathogenic	0.6459	pathogenic	0.055	Stabilizing	1.0	D	0.809	deleterious	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.