TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20979	63160;63161;63162	chr2:178588790;178588789;178588788	chr2:179453517;179453516;179453515
N2AB	19338	58237;58238;58239	chr2:178588790;178588789;178588788	chr2:179453517;179453516;179453515
N2A	18411	55456;55457;55458	chr2:178588790;178588789;178588788	chr2:179453517;179453516;179453515
N2B	11914	35965;35966;35967	chr2:178588790;178588789;178588788	chr2:179453517;179453516;179453515
Novex-1	12039	36340;36341;36342	chr2:178588790;178588789;178588788	chr2:179453517;179453516;179453515
Novex-2	12106	36541;36542;36543	chr2:178588790;178588789;178588788	chr2:179453517;179453516;179453515
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: Fn3-40
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.2278
• 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	rs375728230	-1.029	0.999	N	0.701	0.376	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
E/A	rs375728230	-1.029	0.999	N	0.701	0.376	None	gnomAD-4.0.0	1.36917E-06	None	None	None	None	N	None	2.99007E-05	0	None	0	0	None	0	0	0	0	1.65766E-05
E/D	None	None	0.999	N	0.563	0.203	0.28722502521	gnomAD-4.0.0	2.05318E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7992E-06	0	1.657E-05
E/G	rs375728230	-1.398	1.0	N	0.76	0.385	0.35139820857	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/G	rs375728230	-1.398	1.0	N	0.76	0.385	0.35139820857	gnomAD-4.0.0	6.84584E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99902E-07	0	0
E/K	None	None	0.999	N	0.596	0.366	0.32053947749	gnomAD-4.0.0	6.84585E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99909E-07	0	0
E/Q	rs1306891128	-0.907	1.0	N	0.657	0.273	0.286081765059	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
E/Q	rs1306891128	-0.907	1.0	N	0.657	0.273	0.286081765059	gnomAD-4.0.0	6.84585E-07	None	None	None	None	N	None	0	0	None	0	2.52551E-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	0.2389	likely_benign	0.1729	benign	-0.737	Destabilizing	0.999	D	0.701	prob.neutral	N	0.447946855	None	None	N
E/C	0.8743	likely_pathogenic	0.7987	pathogenic	-0.463	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/D	0.2391	likely_benign	0.1792	benign	-1.329	Destabilizing	0.999	D	0.563	neutral	N	0.493449858	None	None	N
E/F	0.805	likely_pathogenic	0.7078	pathogenic	-0.747	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/G	0.2738	likely_benign	0.1896	benign	-1.065	Destabilizing	1.0	D	0.76	deleterious	N	0.427995657	None	None	N
E/H	0.7335	likely_pathogenic	0.55	ambiguous	-1.131	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
E/I	0.6036	likely_pathogenic	0.4575	ambiguous	0.142	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/K	0.5982	likely_pathogenic	0.3838	ambiguous	-0.741	Destabilizing	0.999	D	0.596	neutral	N	0.48719589	None	None	N
E/L	0.6809	likely_pathogenic	0.5411	ambiguous	0.142	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/M	0.5817	likely_pathogenic	0.455	ambiguous	0.626	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/N	0.4267	ambiguous	0.2924	benign	-0.995	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/P	0.9933	likely_pathogenic	0.9822	pathogenic	-0.129	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/Q	0.2944	likely_benign	0.2024	benign	-0.901	Destabilizing	1.0	D	0.657	neutral	N	0.47740297	None	None	N
E/R	0.7432	likely_pathogenic	0.5339	ambiguous	-0.671	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/S	0.2859	likely_benign	0.1918	benign	-1.344	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
E/T	0.3217	likely_benign	0.2179	benign	-1.075	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/V	0.3796	ambiguous	0.2857	benign	-0.129	Destabilizing	1.0	D	0.795	deleterious	N	0.480059273	None	None	N
E/W	0.9474	likely_pathogenic	0.8987	pathogenic	-0.739	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/Y	0.717	likely_pathogenic	0.5836	pathogenic	-0.546	Destabilizing	1.0	D	0.773	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.