TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5036	15331;15332;15333	chr2:178734818;178734817;178734816	chr2:179599545;179599544;179599543
N2AB	4719	14380;14381;14382	chr2:178734818;178734817;178734816	chr2:179599545;179599544;179599543
N2A	3792	11599;11600;11601	chr2:178734818;178734817;178734816	chr2:179599545;179599544;179599543
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-33
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.379
• 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/G	None	None	0.642	N	0.513	0.255	0.343788945184	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8583E-06	0	0
E/K	rs1353528713	-1.02	0.473	N	0.327	0.245	0.263140351381	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	9.95E-05	0	None	0	None	0	0	0
E/K	rs1353528713	-1.02	0.473	N	0.327	0.245	0.263140351381	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	4.76735E-05	0	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	0.3572	ambiguous	0.3377	benign	-0.896	Destabilizing	0.27	N	0.447	neutral	N	0.512280469	None	None	N
E/C	0.9633	likely_pathogenic	0.9542	pathogenic	-0.656	Destabilizing	0.995	D	0.581	neutral	None	None	None	None	N
E/D	0.2903	likely_benign	0.2907	benign	-1.415	Destabilizing	0.642	D	0.32	neutral	N	0.472334853	None	None	N
E/F	0.8947	likely_pathogenic	0.8941	pathogenic	-0.494	Destabilizing	0.007	N	0.452	neutral	None	None	None	None	N
E/G	0.5753	likely_pathogenic	0.5278	ambiguous	-1.29	Destabilizing	0.642	D	0.513	neutral	N	0.444198534	None	None	N
E/H	0.7107	likely_pathogenic	0.6943	pathogenic	-1.015	Destabilizing	0.944	D	0.491	neutral	None	None	None	None	N
E/I	0.5142	ambiguous	0.4986	ambiguous	0.19	Stabilizing	0.543	D	0.531	neutral	None	None	None	None	N
E/K	0.3396	likely_benign	0.2908	benign	-1.274	Destabilizing	0.473	N	0.327	neutral	N	0.490848369	None	None	N
E/L	0.634	likely_pathogenic	0.6468	pathogenic	0.19	Stabilizing	0.329	N	0.511	neutral	None	None	None	None	N
E/M	0.5927	likely_pathogenic	0.602	pathogenic	0.76	Stabilizing	0.944	D	0.563	neutral	None	None	None	None	N
E/N	0.512	ambiguous	0.5007	ambiguous	-1.581	Destabilizing	0.704	D	0.433	neutral	None	None	None	None	N
E/P	0.9921	likely_pathogenic	0.9893	pathogenic	-0.151	Destabilizing	0.944	D	0.575	neutral	None	None	None	None	N
E/Q	0.2523	likely_benign	0.2362	benign	-1.377	Destabilizing	0.065	N	0.231	neutral	N	0.493792622	None	None	N
E/R	0.5783	likely_pathogenic	0.5163	ambiguous	-1.083	Destabilizing	0.704	D	0.453	neutral	None	None	None	None	N
E/S	0.415	ambiguous	0.4087	ambiguous	-1.977	Destabilizing	0.085	N	0.159	neutral	None	None	None	None	N
E/T	0.4175	ambiguous	0.3789	ambiguous	-1.657	Destabilizing	0.543	D	0.47	neutral	None	None	None	None	N
E/V	0.3039	likely_benign	0.296	benign	-0.151	Destabilizing	0.002	N	0.296	neutral	N	0.420278344	None	None	N
E/W	0.975	likely_pathogenic	0.9723	pathogenic	-0.432	Destabilizing	0.995	D	0.591	neutral	None	None	None	None	N
E/Y	0.8421	likely_pathogenic	0.8344	pathogenic	-0.332	Destabilizing	0.807	D	0.572	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.