TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6142	18649;18650;18651	chr2:178729829;178729828;178729827	chr2:179594556;179594555;179594554
N2AB	5825	17698;17699;17700	chr2:178729829;178729828;178729827	chr2:179594556;179594555;179594554
N2A	4898	14917;14918;14919	chr2:178729829;178729828;178729827	chr2:179594556;179594555;179594554
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-45
• Domain position: 38
• Structural Position: 51
• Q(SASA): 0.579
• 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
D/E	None	None	0.893	N	0.274	0.349	0.221019684889	gnomAD-4.0.0	3.42126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49749E-06	0	0
D/G	None	None	0.998	N	0.642	0.569	0.469989170139	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.1868	likely_benign	0.1933	benign	-0.134	Destabilizing	0.996	D	0.612	neutral	N	0.513090926	None	None	N
D/C	0.6426	likely_pathogenic	0.6488	pathogenic	0.231	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	N
D/E	0.2244	likely_benign	0.2409	benign	-0.129	Destabilizing	0.893	D	0.274	neutral	N	0.508785536	None	None	N
D/F	0.6286	likely_pathogenic	0.6228	pathogenic	-0.177	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
D/G	0.1315	likely_benign	0.1358	benign	-0.292	Destabilizing	0.998	D	0.642	neutral	N	0.505243798	None	None	N
D/H	0.2486	likely_benign	0.255	benign	0.043	Stabilizing	1.0	D	0.645	neutral	D	0.534993843	None	None	N
D/I	0.6198	likely_pathogenic	0.6148	pathogenic	0.226	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
D/K	0.3585	ambiguous	0.3629	ambiguous	0.625	Stabilizing	0.999	D	0.658	neutral	None	None	None	None	N
D/L	0.4489	ambiguous	0.4452	ambiguous	0.226	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
D/M	0.7078	likely_pathogenic	0.7101	pathogenic	0.34	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
D/N	0.0879	likely_benign	0.0896	benign	0.327	Stabilizing	0.999	D	0.609	neutral	N	0.435554427	None	None	N
D/P	0.8773	likely_pathogenic	0.8833	pathogenic	0.127	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
D/Q	0.3282	likely_benign	0.3464	ambiguous	0.353	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	N
D/R	0.324	likely_benign	0.3304	benign	0.684	Stabilizing	0.999	D	0.664	neutral	None	None	None	None	N
D/S	0.1478	likely_benign	0.1545	benign	0.249	Stabilizing	0.997	D	0.584	neutral	None	None	None	None	N
D/T	0.4533	ambiguous	0.4664	ambiguous	0.379	Stabilizing	1.0	D	0.656	neutral	None	None	None	None	N
D/V	0.3995	ambiguous	0.3929	ambiguous	0.127	Stabilizing	0.999	D	0.696	prob.neutral	D	0.535500822	None	None	N
D/W	0.8387	likely_pathogenic	0.8395	pathogenic	-0.089	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
D/Y	0.2175	likely_benign	0.2122	benign	0.06	Stabilizing	1.0	D	0.679	prob.neutral	D	0.553605077	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.