TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21102	63529;63530;63531	chr2:178588103;178588102;178588101	chr2:179452830;179452829;179452828
N2AB	19461	58606;58607;58608	chr2:178588103;178588102;178588101	chr2:179452830;179452829;179452828
N2A	18534	55825;55826;55827	chr2:178588103;178588102;178588101	chr2:179452830;179452829;179452828
N2B	12037	36334;36335;36336	chr2:178588103;178588102;178588101	chr2:179452830;179452829;179452828
Novex-1	12162	36709;36710;36711	chr2:178588103;178588102;178588101	chr2:179452830;179452829;179452828
Novex-2	12229	36910;36911;36912	chr2:178588103;178588102;178588101	chr2:179452830;179452829;179452828
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-41
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1382
• 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	rs1201894498	-1.923	0.104	N	0.31	0.131	0.190952846119	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs1201894498	-1.923	0.104	N	0.31	0.131	0.190952846119	gnomAD-4.0.0	1.59315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43361E-05	0
E/K	rs1343764526	None	0.994	N	0.676	0.425	0.346768085243	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1343764526	None	0.994	N	0.676	0.425	0.346768085243	gnomAD-4.0.0	3.10022E-06	None	None	None	None	N	None	1.33583E-05	0	None	0	0	None	0	0	3.39177E-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	0.7611	likely_pathogenic	0.7867	pathogenic	-1.822	Destabilizing	0.994	D	0.646	neutral	D	0.523012205	None	None	N
E/C	0.9727	likely_pathogenic	0.9729	pathogenic	-1.132	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/D	0.6445	likely_pathogenic	0.6136	pathogenic	-1.699	Destabilizing	0.104	N	0.31	neutral	N	0.468952929	None	None	N
E/F	0.9685	likely_pathogenic	0.962	pathogenic	-1.484	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/G	0.8459	likely_pathogenic	0.8541	pathogenic	-2.208	Highly Destabilizing	0.994	D	0.678	prob.neutral	N	0.520013691	None	None	N
E/H	0.9331	likely_pathogenic	0.9238	pathogenic	-1.511	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/I	0.9426	likely_pathogenic	0.9471	pathogenic	-0.711	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
E/K	0.8796	likely_pathogenic	0.8852	pathogenic	-2.046	Highly Destabilizing	0.994	D	0.676	prob.neutral	N	0.505615512	None	None	N
E/L	0.925	likely_pathogenic	0.9213	pathogenic	-0.711	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/M	0.9109	likely_pathogenic	0.9119	pathogenic	0.077	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/N	0.9319	likely_pathogenic	0.9275	pathogenic	-2.18	Highly Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
E/P	0.9989	likely_pathogenic	0.999	pathogenic	-1.068	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Q	0.4917	ambiguous	0.5052	ambiguous	-1.886	Destabilizing	0.998	D	0.776	deleterious	D	0.524618127	None	None	N
E/R	0.9034	likely_pathogenic	0.9041	pathogenic	-1.797	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
E/S	0.805	likely_pathogenic	0.8116	pathogenic	-2.847	Highly Destabilizing	0.992	D	0.675	prob.neutral	None	None	None	None	N
E/T	0.897	likely_pathogenic	0.903	pathogenic	-2.495	Highly Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
E/V	0.8621	likely_pathogenic	0.875	pathogenic	-1.068	Destabilizing	0.999	D	0.767	deleterious	N	0.512416368	None	None	N
E/W	0.987	likely_pathogenic	0.9828	pathogenic	-1.551	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Y	0.9534	likely_pathogenic	0.942	pathogenic	-1.352	Destabilizing	1.0	D	0.814	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.