TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17101	51526;51527;51528	chr2:178610225;178610224;178610223	chr2:179474952;179474951;179474950
N2AB	15460	46603;46604;46605	chr2:178610225;178610224;178610223	chr2:179474952;179474951;179474950
N2A	14533	43822;43823;43824	chr2:178610225;178610224;178610223	chr2:179474952;179474951;179474950
N2B	8036	24331;24332;24333	chr2:178610225;178610224;178610223	chr2:179474952;179474951;179474950
Novex-1	8161	24706;24707;24708	chr2:178610225;178610224;178610223	chr2:179474952;179474951;179474950
Novex-2	8228	24907;24908;24909	chr2:178610225;178610224;178610223	chr2:179474952;179474951;179474950
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: Fn3-12
• Domain position: 55
• Structural Position: 77
• Q(SASA): 0.0512
• 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/D	rs1406870908	None	0.999	N	0.611	0.154	0.228597637076	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/D	rs1406870908	None	0.999	N	0.611	0.154	0.228597637076	gnomAD-4.0.0	6.58198E-06	None	None	None	None	N	None	0	6.56426E-05	None	0	0	None	0	0	0	0	0
E/K	None	None	0.999	N	0.637	0.376	0.341934017632	gnomAD-4.0.0	1.59277E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-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
E/A	0.3342	likely_benign	0.373	ambiguous	-0.75	Destabilizing	0.999	D	0.675	prob.neutral	N	0.44788814	None	None	N
E/C	0.9285	likely_pathogenic	0.9403	pathogenic	-0.445	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/D	0.1727	likely_benign	0.1815	benign	-1.059	Destabilizing	0.999	D	0.611	neutral	N	0.489140117	None	None	N
E/F	0.9067	likely_pathogenic	0.9298	pathogenic	-0.009	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/G	0.3671	ambiguous	0.3974	ambiguous	-1.129	Destabilizing	1.0	D	0.742	deleterious	N	0.414524928	None	None	N
E/H	0.7598	likely_pathogenic	0.7988	pathogenic	-0.143	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/I	0.5612	ambiguous	0.6092	pathogenic	0.291	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/K	0.3524	ambiguous	0.3874	ambiguous	-0.464	Destabilizing	0.999	D	0.637	neutral	N	0.493679145	None	None	N
E/L	0.7075	likely_pathogenic	0.7599	pathogenic	0.291	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/M	0.6876	likely_pathogenic	0.7383	pathogenic	0.634	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/N	0.4025	ambiguous	0.4477	ambiguous	-1.076	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/P	0.8742	likely_pathogenic	0.8759	pathogenic	-0.034	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.2554	likely_benign	0.2899	benign	-0.901	Destabilizing	1.0	D	0.698	prob.neutral	N	0.513651772	None	None	N
E/R	0.5963	likely_pathogenic	0.6466	pathogenic	-0.102	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/S	0.379	ambiguous	0.422	ambiguous	-1.359	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
E/T	0.4183	ambiguous	0.4603	ambiguous	-1.032	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/V	0.3734	ambiguous	0.4175	ambiguous	-0.034	Destabilizing	1.0	D	0.769	deleterious	N	0.381108574	None	None	N
E/W	0.9745	likely_pathogenic	0.9821	pathogenic	0.296	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/Y	0.848	likely_pathogenic	0.882	pathogenic	0.266	Stabilizing	1.0	D	0.809	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.