TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31273	94042;94043;94044	chr2:178547809;178547808;178547807	chr2:179412536;179412535;179412534
N2AB	29632	89119;89120;89121	chr2:178547809;178547808;178547807	chr2:179412536;179412535;179412534
N2A	28705	86338;86339;86340	chr2:178547809;178547808;178547807	chr2:179412536;179412535;179412534
N2B	22208	66847;66848;66849	chr2:178547809;178547808;178547807	chr2:179412536;179412535;179412534
Novex-1	22333	67222;67223;67224	chr2:178547809;178547808;178547807	chr2:179412536;179412535;179412534
Novex-2	22400	67423;67424;67425	chr2:178547809;178547808;178547807	chr2:179412536;179412535;179412534
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-151
• Domain position: 56
• Structural Position: 138
• Q(SASA): 0.0988
• 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
L/Q	None	None	1.0	D	0.854	0.695	0.86173524933	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
L/V	rs1697833909	None	0.999	N	0.651	0.466	0.586144602217	gnomAD-4.0.0	3.18224E-06	None	None	None	None	N	None	0	0	None	0	5.54847E-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
L/A	0.89	likely_pathogenic	0.9275	pathogenic	-2.38	Highly Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
L/C	0.837	likely_pathogenic	0.8537	pathogenic	-1.903	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9996	pathogenic	-2.962	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/E	0.9944	likely_pathogenic	0.9965	pathogenic	-2.622	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/F	0.3924	ambiguous	0.4285	ambiguous	-1.448	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/G	0.9837	likely_pathogenic	0.9909	pathogenic	-3.009	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/H	0.9737	likely_pathogenic	0.9819	pathogenic	-2.972	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/I	0.1661	likely_benign	0.1883	benign	-0.478	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
L/K	0.9854	likely_pathogenic	0.9897	pathogenic	-1.724	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/M	0.2704	likely_benign	0.2992	benign	-0.879	Destabilizing	1.0	D	0.782	deleterious	D	0.537347246	None	None	N
L/N	0.9952	likely_pathogenic	0.9971	pathogenic	-2.471	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/P	0.9945	likely_pathogenic	0.997	pathogenic	-1.104	Destabilizing	1.0	D	0.858	deleterious	D	0.550224489	None	None	N
L/Q	0.9709	likely_pathogenic	0.9806	pathogenic	-2.022	Highly Destabilizing	1.0	D	0.854	deleterious	D	0.550224489	None	None	N
L/R	0.9651	likely_pathogenic	0.9745	pathogenic	-2.063	Highly Destabilizing	1.0	D	0.85	deleterious	D	0.550224489	None	None	N
L/S	0.9882	likely_pathogenic	0.9931	pathogenic	-3.03	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/T	0.9634	likely_pathogenic	0.976	pathogenic	-2.503	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
L/V	0.1817	likely_benign	0.198	benign	-1.104	Destabilizing	0.999	D	0.651	neutral	N	0.510595711	None	None	N
L/W	0.8875	likely_pathogenic	0.912	pathogenic	-1.786	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/Y	0.9022	likely_pathogenic	0.9132	pathogenic	-1.584	Destabilizing	1.0	D	0.795	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.