TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6878	20857;20858;20859	chr2:178725572;178725571;178725570	chr2:179590299;179590298;179590297
N2AB	6561	19906;19907;19908	chr2:178725572;178725571;178725570	chr2:179590299;179590298;179590297
N2A	5634	17125;17126;17127	chr2:178725572;178725571;178725570	chr2:179590299;179590298;179590297
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-53
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4337
• 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	rs752107739	-0.622	0.961	D	0.446	0.319	0.513901218509	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/A	rs752107739	-0.622	0.961	D	0.446	0.319	0.513901218509	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/A	rs752107739	-0.622	0.961	D	0.446	0.319	0.513901218509	gnomAD-4.0.0	1.66744E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.11419E-05	0	0
E/Q	rs755499713	-0.085	0.961	N	0.44	0.253	0.340273420219	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/Q	rs755499713	-0.085	0.961	N	0.44	0.253	0.340273420219	gnomAD-4.0.0	1.59421E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86261E-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	0.1809	likely_benign	0.1524	benign	-0.64	Destabilizing	0.961	D	0.446	neutral	D	0.533155545	None	None	N
E/C	0.8844	likely_pathogenic	0.8611	pathogenic	-0.187	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/D	0.2417	likely_benign	0.2238	benign	-0.572	Destabilizing	0.98	D	0.396	neutral	N	0.485936727	None	None	N
E/F	0.7762	likely_pathogenic	0.754	pathogenic	-0.355	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
E/G	0.294	likely_benign	0.2564	benign	-0.886	Destabilizing	0.98	D	0.511	neutral	N	0.491723625	None	None	N
E/H	0.4747	ambiguous	0.4634	ambiguous	-0.249	Destabilizing	0.999	D	0.502	neutral	None	None	None	None	N
E/I	0.3939	ambiguous	0.3724	ambiguous	-0.006	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/K	0.1547	likely_benign	0.1517	benign	0.116	Stabilizing	0.122	N	0.146	neutral	N	0.471760369	None	None	N
E/L	0.4687	ambiguous	0.4376	ambiguous	-0.006	Destabilizing	0.996	D	0.565	neutral	None	None	None	None	N
E/M	0.5154	ambiguous	0.4859	ambiguous	0.195	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
E/N	0.4229	ambiguous	0.3829	ambiguous	-0.322	Destabilizing	0.985	D	0.459	neutral	None	None	None	None	N
E/P	0.963	likely_pathogenic	0.9648	pathogenic	-0.197	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
E/Q	0.133	likely_benign	0.1284	benign	-0.276	Destabilizing	0.961	D	0.44	neutral	N	0.493165203	None	None	N
E/R	0.2581	likely_benign	0.2567	benign	0.364	Stabilizing	0.942	D	0.407	neutral	None	None	None	None	N
E/S	0.2231	likely_benign	0.1924	benign	-0.502	Destabilizing	0.97	D	0.404	neutral	None	None	None	None	N
E/T	0.2238	likely_benign	0.2005	benign	-0.299	Destabilizing	0.985	D	0.501	neutral	None	None	None	None	N
E/V	0.2309	likely_benign	0.2152	benign	-0.197	Destabilizing	0.994	D	0.525	neutral	D	0.537158642	None	None	N
E/W	0.9064	likely_pathogenic	0.9071	pathogenic	-0.12	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
E/Y	0.6895	likely_pathogenic	0.6723	pathogenic	-0.092	Destabilizing	0.999	D	0.649	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.