TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21192	63799;63800;63801	chr2:178587735;178587734;178587733	chr2:179452462;179452461;179452460
N2AB	19551	58876;58877;58878	chr2:178587735;178587734;178587733	chr2:179452462;179452461;179452460
N2A	18624	56095;56096;56097	chr2:178587735;178587734;178587733	chr2:179452462;179452461;179452460
N2B	12127	36604;36605;36606	chr2:178587735;178587734;178587733	chr2:179452462;179452461;179452460
Novex-1	12252	36979;36980;36981	chr2:178587735;178587734;178587733	chr2:179452462;179452461;179452460
Novex-2	12319	37180;37181;37182	chr2:178587735;178587734;178587733	chr2:179452462;179452461;179452460
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-123
• Domain position: 16
• Structural Position: 28
• Q(SASA): 0.1835
• 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
I/V	rs758357424	-1.013	0.993	N	0.359	0.24	0.366277470483	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
I/V	rs758357424	-1.013	0.993	N	0.359	0.24	0.366277470483	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
I/V	rs758357424	-1.013	0.993	N	0.359	0.24	0.366277470483	gnomAD-4.0.0	1.97371E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.41462E-05	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
I/A	0.9625	likely_pathogenic	0.9638	pathogenic	-2.771	Highly Destabilizing	0.999	D	0.611	neutral	None	None	None	None	I
I/C	0.9779	likely_pathogenic	0.9816	pathogenic	-2.075	Highly Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
I/D	0.9994	likely_pathogenic	0.9992	pathogenic	-3.278	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
I/E	0.998	likely_pathogenic	0.9974	pathogenic	-3.015	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
I/F	0.7411	likely_pathogenic	0.7123	pathogenic	-1.653	Destabilizing	1.0	D	0.764	deleterious	N	0.511928471	None	None	I
I/G	0.9967	likely_pathogenic	0.9964	pathogenic	-3.357	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
I/H	0.9973	likely_pathogenic	0.9968	pathogenic	-2.825	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
I/K	0.9964	likely_pathogenic	0.9954	pathogenic	-2.396	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
I/L	0.2256	likely_benign	0.2204	benign	-1.054	Destabilizing	0.993	D	0.398	neutral	N	0.382478719	None	None	I
I/M	0.3946	ambiguous	0.3926	ambiguous	-0.971	Destabilizing	1.0	D	0.761	deleterious	N	0.463302664	None	None	I
I/N	0.9923	likely_pathogenic	0.9908	pathogenic	-2.851	Highly Destabilizing	1.0	D	0.839	deleterious	N	0.49787856	None	None	I
I/P	0.9957	likely_pathogenic	0.9947	pathogenic	-1.61	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
I/Q	0.9948	likely_pathogenic	0.9933	pathogenic	-2.652	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
I/R	0.9945	likely_pathogenic	0.9922	pathogenic	-2.114	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
I/S	0.9861	likely_pathogenic	0.985	pathogenic	-3.532	Highly Destabilizing	1.0	D	0.802	deleterious	N	0.486268765	None	None	I
I/T	0.9771	likely_pathogenic	0.9781	pathogenic	-3.112	Highly Destabilizing	1.0	D	0.793	deleterious	N	0.515507494	None	None	I
I/V	0.1499	likely_benign	0.1763	benign	-1.61	Destabilizing	0.993	D	0.359	neutral	N	0.459147205	None	None	I
I/W	0.9963	likely_pathogenic	0.9957	pathogenic	-2.091	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
I/Y	0.9862	likely_pathogenic	0.9833	pathogenic	-1.812	Destabilizing	1.0	D	0.817	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.