TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30407	91444;91445;91446	chr2:178551681;178551680;178551679	chr2:179416408;179416407;179416406
N2AB	28766	86521;86522;86523	chr2:178551681;178551680;178551679	chr2:179416408;179416407;179416406
N2A	27839	83740;83741;83742	chr2:178551681;178551680;178551679	chr2:179416408;179416407;179416406
N2B	21342	64249;64250;64251	chr2:178551681;178551680;178551679	chr2:179416408;179416407;179416406
Novex-1	21467	64624;64625;64626	chr2:178551681;178551680;178551679	chr2:179416408;179416407;179416406
Novex-2	21534	64825;64826;64827	chr2:178551681;178551680;178551679	chr2:179416408;179416407;179416406
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-109
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3389
• 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
L/P	rs778086508	-1.341	1.0	N	0.831	0.435	0.80318517577	gnomAD-2.1.1	8.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.59E-05	None	0	0	0
L/P	rs778086508	-1.341	1.0	N	0.831	0.435	0.80318517577	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs778086508	-1.341	1.0	N	0.831	0.435	0.80318517577	gnomAD-4.0.0	1.02815E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.40269E-06	9.41772E-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
L/A	0.1876	likely_benign	0.2092	benign	-1.861	Destabilizing	0.994	D	0.721	prob.delet.	None	None	None	None	I
L/C	0.3212	likely_benign	0.3522	ambiguous	-0.956	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
L/D	0.6198	likely_pathogenic	0.6508	pathogenic	-0.877	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
L/E	0.3324	likely_benign	0.3499	ambiguous	-0.848	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
L/F	0.0935	likely_benign	0.1026	benign	-1.276	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	I
L/G	0.4461	ambiguous	0.4757	ambiguous	-2.215	Highly Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
L/H	0.1928	likely_benign	0.2197	benign	-1.264	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
L/I	0.0671	likely_benign	0.0684	benign	-0.944	Destabilizing	0.984	D	0.641	neutral	N	0.419125458	None	None	I
L/K	0.1892	likely_benign	0.21	benign	-1.061	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
L/M	0.0901	likely_benign	0.092	benign	-0.661	Destabilizing	0.971	D	0.547	neutral	None	None	None	None	I
L/N	0.285	likely_benign	0.3136	benign	-0.829	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
L/P	0.2078	likely_benign	0.2473	benign	-1.22	Destabilizing	1.0	D	0.831	deleterious	N	0.468572843	None	None	I
L/Q	0.132	likely_benign	0.1512	benign	-0.981	Destabilizing	0.999	D	0.84	deleterious	N	0.455411545	None	None	I
L/R	0.1614	likely_benign	0.184	benign	-0.474	Destabilizing	0.999	D	0.843	deleterious	N	0.467514051	None	None	I
L/S	0.2116	likely_benign	0.2389	benign	-1.557	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
L/T	0.149	likely_benign	0.1691	benign	-1.403	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	I
L/V	0.0719	likely_benign	0.0763	benign	-1.22	Destabilizing	0.984	D	0.679	prob.neutral	N	0.412756846	None	None	I
L/W	0.2202	likely_benign	0.2309	benign	-1.301	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
L/Y	0.2262	likely_benign	0.2444	benign	-1.109	Destabilizing	1.0	D	0.834	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.