TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22127	66604;66605;66606	chr2:178581990;178581989;178581988	chr2:179446717;179446716;179446715
N2AB	20486	61681;61682;61683	chr2:178581990;178581989;178581988	chr2:179446717;179446716;179446715
N2A	19559	58900;58901;58902	chr2:178581990;178581989;178581988	chr2:179446717;179446716;179446715
N2B	13062	39409;39410;39411	chr2:178581990;178581989;178581988	chr2:179446717;179446716;179446715
Novex-1	13187	39784;39785;39786	chr2:178581990;178581989;178581988	chr2:179446717;179446716;179446715
Novex-2	13254	39985;39986;39987	chr2:178581990;178581989;178581988	chr2:179446717;179446716;179446715
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: Fn3-48
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1904
• 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/A	rs1289473781	-1.529	0.958	N	0.55	0.461	0.365317461125	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/A	rs1289473781	-1.529	0.958	N	0.55	0.461	0.365317461125	gnomAD-4.0.0	3.18454E-06	None	None	None	None	N	None	0	4.57436E-05	None	0	0	None	0	0	0	0	0
E/D	rs1208330464	-1.481	0.958	N	0.483	0.268	0.282575091529	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
E/D	rs1208330464	-1.481	0.958	N	0.483	0.268	0.282575091529	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	0	None	0	2.77793E-05	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	0.5508	ambiguous	0.5806	pathogenic	-1.725	Destabilizing	0.958	D	0.55	neutral	N	0.483284976	None	None	N
E/C	0.9418	likely_pathogenic	0.9473	pathogenic	-0.897	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/D	0.8546	likely_pathogenic	0.8172	pathogenic	-1.561	Destabilizing	0.958	D	0.483	neutral	N	0.482728771	None	None	N
E/F	0.9669	likely_pathogenic	0.9654	pathogenic	-1.378	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
E/G	0.8534	likely_pathogenic	0.8591	pathogenic	-2.134	Highly Destabilizing	0.988	D	0.673	neutral	N	0.507011544	None	None	N
E/H	0.9233	likely_pathogenic	0.9147	pathogenic	-1.275	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
E/I	0.6579	likely_pathogenic	0.6904	pathogenic	-0.551	Destabilizing	0.995	D	0.832	deleterious	None	None	None	None	N
E/K	0.7729	likely_pathogenic	0.7778	pathogenic	-1.399	Destabilizing	0.919	D	0.503	neutral	N	0.506899158	None	None	N
E/L	0.8116	likely_pathogenic	0.8168	pathogenic	-0.551	Destabilizing	0.991	D	0.751	deleterious	None	None	None	None	N
E/M	0.7649	likely_pathogenic	0.7835	pathogenic	0.213	Stabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
E/N	0.9117	likely_pathogenic	0.9035	pathogenic	-1.65	Destabilizing	0.991	D	0.68	prob.neutral	None	None	None	None	N
E/P	0.9988	likely_pathogenic	0.9988	pathogenic	-0.928	Destabilizing	0.995	D	0.738	prob.delet.	None	None	None	None	N
E/Q	0.2663	likely_benign	0.2759	benign	-1.402	Destabilizing	0.414	N	0.348	neutral	N	0.444850622	None	None	N
E/R	0.827	likely_pathogenic	0.8237	pathogenic	-1.193	Destabilizing	0.982	D	0.676	prob.neutral	None	None	None	None	N
E/S	0.7038	likely_pathogenic	0.7144	pathogenic	-2.37	Highly Destabilizing	0.968	D	0.538	neutral	None	None	None	None	N
E/T	0.6965	likely_pathogenic	0.722	pathogenic	-1.977	Destabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	N
E/V	0.5278	ambiguous	0.5545	ambiguous	-0.928	Destabilizing	0.988	D	0.723	prob.delet.	N	0.467623029	None	None	N
E/W	0.994	likely_pathogenic	0.9931	pathogenic	-1.314	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/Y	0.9586	likely_pathogenic	0.9547	pathogenic	-1.128	Destabilizing	0.998	D	0.801	deleterious	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.