TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10119	30580;30581;30582	chr2:178702532;178702531;178702530	chr2:179567259;179567258;179567257
N2AB	9802	29629;29630;29631	chr2:178702532;178702531;178702530	chr2:179567259;179567258;179567257
N2A	8875	26848;26849;26850	chr2:178702532;178702531;178702530	chr2:179567259;179567258;179567257
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-86
• Domain position: 42
• Structural Position: 70
• Q(SASA): 0.5888
• 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
E/Q	rs778565859	0.129	1.0	None	0.527	0.256	0.475034548194	gnomAD-2.1.1	9.23E-05	None	None	None	None	N	None	0	6.66126E-04	None	0	0	None	0	None	0	0	0
E/Q	rs778565859	0.129	1.0	None	0.527	0.256	0.475034548194	gnomAD-4.0.0	1.64192E-05	None	None	None	None	N	None	0	4.91906E-04	None	0	0	None	0	0	1.79878E-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
E/A	0.4962	ambiguous	0.4495	ambiguous	-0.68	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
E/C	0.9937	likely_pathogenic	0.9914	pathogenic	-0.168	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
E/D	0.7433	likely_pathogenic	0.7437	pathogenic	-0.422	Destabilizing	0.999	D	0.443	neutral	None	None	None	None	N
E/F	0.9937	likely_pathogenic	0.9915	pathogenic	-0.345	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
E/G	0.682	likely_pathogenic	0.6353	pathogenic	-0.911	Destabilizing	1.0	D	0.58	neutral	None	None	None	None	N
E/H	0.9679	likely_pathogenic	0.9626	pathogenic	-0.16	Destabilizing	1.0	D	0.592	neutral	None	None	None	None	N
E/I	0.9508	likely_pathogenic	0.9334	pathogenic	-0.086	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
E/K	0.7307	likely_pathogenic	0.6746	pathogenic	0.236	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	N
E/L	0.9536	likely_pathogenic	0.9378	pathogenic	-0.086	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
E/M	0.9564	likely_pathogenic	0.9403	pathogenic	0.118	Stabilizing	1.0	D	0.578	neutral	None	None	None	None	N
E/N	0.8979	likely_pathogenic	0.8772	pathogenic	-0.302	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
E/P	0.7904	likely_pathogenic	0.7435	pathogenic	-0.265	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
E/Q	0.5654	likely_pathogenic	0.5285	ambiguous	-0.22	Destabilizing	1.0	D	0.527	neutral	None	None	None	None	N
E/R	0.8384	likely_pathogenic	0.8013	pathogenic	0.46	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
E/S	0.7399	likely_pathogenic	0.7132	pathogenic	-0.437	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
E/T	0.8404	likely_pathogenic	0.8051	pathogenic	-0.232	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
E/V	0.8395	likely_pathogenic	0.8049	pathogenic	-0.265	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
E/W	0.9981	likely_pathogenic	0.9977	pathogenic	-0.083	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/Y	0.9866	likely_pathogenic	0.9831	pathogenic	-0.079	Destabilizing	1.0	D	0.596	neutral	None	None	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.