TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8070	24433;24434;24435	chr2:178719182;178719181;178719180	chr2:179583909;179583908;179583907
N2AB	7753	23482;23483;23484	chr2:178719182;178719181;178719180	chr2:179583909;179583908;179583907
N2A	6826	20701;20702;20703	chr2:178719182;178719181;178719180	chr2:179583909;179583908;179583907
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-65
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1378
• 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
A/E	rs796067887	-1.302	0.059	D	0.49	0.497	0.470810165807	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	1.14705E-04	0	None	0	0	None	0	None	0	0	0
A/E	rs796067887	-1.302	0.059	D	0.49	0.497	0.470810165807	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/E	rs796067887	-1.302	0.059	D	0.49	0.497	0.470810165807	gnomAD-4.0.0	6.5716E-06	None	None	None	None	I	None	2.41231E-05	0	None	0	0	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
A/C	0.6645	likely_pathogenic	0.6901	pathogenic	-1.159	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	I
A/D	0.8593	likely_pathogenic	0.8712	pathogenic	-1.418	Destabilizing	0.851	D	0.776	deleterious	None	None	None	None	I
A/E	0.8747	likely_pathogenic	0.8714	pathogenic	-1.387	Destabilizing	0.059	N	0.49	neutral	D	0.550826238	None	None	I
A/F	0.8148	likely_pathogenic	0.8373	pathogenic	-1.005	Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	I
A/G	0.1757	likely_benign	0.1945	benign	-1.336	Destabilizing	0.011	N	0.273	neutral	N	0.491082196	None	None	I
A/H	0.9232	likely_pathogenic	0.9274	pathogenic	-1.562	Destabilizing	0.997	D	0.761	deleterious	None	None	None	None	I
A/I	0.6264	likely_pathogenic	0.6683	pathogenic	-0.237	Destabilizing	0.976	D	0.781	deleterious	None	None	None	None	I
A/K	0.9392	likely_pathogenic	0.9343	pathogenic	-1.234	Destabilizing	0.851	D	0.771	deleterious	None	None	None	None	I
A/L	0.5473	ambiguous	0.5869	pathogenic	-0.237	Destabilizing	0.919	D	0.764	deleterious	None	None	None	None	I
A/M	0.5239	ambiguous	0.5635	ambiguous	-0.29	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	I
A/N	0.798	likely_pathogenic	0.8193	pathogenic	-1.118	Destabilizing	0.976	D	0.776	deleterious	None	None	None	None	I
A/P	0.9745	likely_pathogenic	0.9747	pathogenic	-0.45	Destabilizing	0.984	D	0.774	deleterious	D	0.551079727	None	None	I
A/Q	0.8689	likely_pathogenic	0.8631	pathogenic	-1.183	Destabilizing	0.952	D	0.786	deleterious	None	None	None	None	I
A/R	0.8792	likely_pathogenic	0.8666	pathogenic	-1.021	Destabilizing	0.976	D	0.775	deleterious	None	None	None	None	I
A/S	0.1465	likely_benign	0.1523	benign	-1.548	Destabilizing	0.811	D	0.615	neutral	D	0.525501641	None	None	I
A/T	0.1576	likely_benign	0.1681	benign	-1.405	Destabilizing	0.211	N	0.429	neutral	N	0.504209247	None	None	I
A/V	0.2989	likely_benign	0.3168	benign	-0.45	Destabilizing	0.896	D	0.663	neutral	N	0.515185859	None	None	I
A/W	0.9734	likely_pathogenic	0.9782	pathogenic	-1.447	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	I
A/Y	0.902	likely_pathogenic	0.9177	pathogenic	-0.989	Destabilizing	0.996	D	0.779	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.