TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9417	28474;28475;28476	chr2:178710848;178710847;178710846	chr2:179575575;179575574;179575573
N2AB	9100	27523;27524;27525	chr2:178710848;178710847;178710846	chr2:179575575;179575574;179575573
N2A	8173	24742;24743;24744	chr2:178710848;178710847;178710846	chr2:179575575;179575574;179575573
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-80
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4355
• Predicted PPI site: I

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	rs773169301	-0.89	0.998	None	0.47	0.287	0.293147016451	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	1.11309E-04	None	0	None	0	0	0
E/D	rs773169301	-0.89	0.998	None	0.47	0.287	0.293147016451	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	3.85356E-04	None	0	0	0	0	0
E/D	rs773169301	-0.89	0.998	None	0.47	0.287	0.293147016451	gnomAD-4.0.0	3.09838E-06	None	None	None	None	I	None	0	0	None	0	1.11388E-04	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	0.1564	likely_benign	0.2091	benign	-0.831	Destabilizing	0.996	D	0.614	neutral	None	None	None	None	I
E/C	0.8228	likely_pathogenic	0.9113	pathogenic	-0.453	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/D	0.2077	likely_benign	0.2957	benign	-1.097	Destabilizing	0.998	D	0.47	neutral	None	None	None	None	I
E/F	0.6297	likely_pathogenic	0.7856	pathogenic	-0.4	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
E/G	0.2365	likely_benign	0.3377	benign	-1.189	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
E/H	0.3217	likely_benign	0.5399	ambiguous	-0.786	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
E/I	0.27	likely_benign	0.3943	ambiguous	0.142	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
E/K	0.1171	likely_benign	0.2077	benign	-0.798	Destabilizing	0.992	D	0.524	neutral	None	None	None	None	I
E/L	0.3367	likely_benign	0.4979	ambiguous	0.142	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/M	0.3996	ambiguous	0.5465	ambiguous	0.62	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
E/N	0.3035	likely_benign	0.4543	ambiguous	-1.147	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/P	0.8973	likely_pathogenic	0.9433	pathogenic	-0.161	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
E/Q	0.0967	likely_benign	0.1541	benign	-0.998	Destabilizing	0.957	D	0.354	neutral	None	None	None	None	I
E/R	0.172	likely_benign	0.3145	benign	-0.564	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
E/S	0.1749	likely_benign	0.2556	benign	-1.458	Destabilizing	0.997	D	0.595	neutral	None	None	None	None	I
E/T	0.1703	likely_benign	0.243	benign	-1.17	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
E/V	0.183	likely_benign	0.2434	benign	-0.161	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	I
E/W	0.8399	likely_pathogenic	0.9363	pathogenic	-0.225	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
E/Y	0.5479	ambiguous	0.7454	pathogenic	-0.193	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I

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.