TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6356	19291;19292;19293	chr2:178728972;178728971;178728970	chr2:179593699;179593698;179593697
N2AB	6039	18340;18341;18342	chr2:178728972;178728971;178728970	chr2:179593699;179593698;179593697
N2A	5112	15559;15560;15561	chr2:178728972;178728971;178728970	chr2:179593699;179593698;179593697
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-47
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.7232
• 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
N/I	rs773854949	0.406	0.178	N	0.237	0.158	None	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
N/I	rs773854949	0.406	0.178	N	0.237	0.158	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/I	rs773854949	0.406	0.178	N	0.237	0.158	None	gnomAD-4.0.0	7.43953E-06	None	None	None	None	N	None	1.33515E-05	0	None	0	0	None	0	0	9.32554E-06	0	0
N/S	None	None	0.017	N	0.057	0.1	0.0611884634855	gnomAD-4.0.0	6.84532E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99651E-07	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
N/A	0.1101	likely_benign	0.0909	benign	-0.413	Destabilizing	0.003	N	0.101	neutral	None	None	None	None	N
N/C	0.1982	likely_benign	0.1558	benign	0.329	Stabilizing	0.968	D	0.343	neutral	None	None	None	None	N
N/D	0.0955	likely_benign	0.0848	benign	0.115	Stabilizing	0.302	N	0.147	neutral	N	0.406049012	None	None	N
N/E	0.1937	likely_benign	0.1567	benign	0.089	Stabilizing	0.365	N	0.173	neutral	None	None	None	None	N
N/F	0.285	likely_benign	0.2274	benign	-0.736	Destabilizing	0.41	N	0.397	neutral	None	None	None	None	N
N/G	0.1594	likely_benign	0.1312	benign	-0.602	Destabilizing	0.2	N	0.166	neutral	None	None	None	None	N
N/H	0.0776	likely_benign	0.0715	benign	-0.616	Destabilizing	0.882	D	0.189	neutral	N	0.4086466	None	None	N
N/I	0.0992	likely_benign	0.08	benign	None	Stabilizing	0.178	N	0.237	neutral	N	0.373032517	None	None	N
N/K	0.1256	likely_benign	0.1068	benign	0.061	Stabilizing	0.302	N	0.169	neutral	N	0.358063064	None	None	N
N/L	0.1251	likely_benign	0.1064	benign	None	Stabilizing	0.002	N	0.141	neutral	None	None	None	None	N
N/M	0.1967	likely_benign	0.1598	benign	0.362	Stabilizing	0.83	D	0.367	neutral	None	None	None	None	N
N/P	0.2415	likely_benign	0.1965	benign	-0.11	Destabilizing	0.738	D	0.364	neutral	None	None	None	None	N
N/Q	0.1879	likely_benign	0.1528	benign	-0.395	Destabilizing	0.738	D	0.154	neutral	None	None	None	None	N
N/R	0.1323	likely_benign	0.1153	benign	0.1	Stabilizing	0.738	D	0.152	neutral	None	None	None	None	N
N/S	0.063	likely_benign	0.0587	benign	-0.191	Destabilizing	0.017	N	0.057	neutral	N	0.324817282	None	None	N
N/T	0.0844	likely_benign	0.0734	benign	-0.066	Destabilizing	0.006	N	0.058	neutral	N	0.330204459	None	None	N
N/V	0.1118	likely_benign	0.0911	benign	-0.11	Destabilizing	0.008	N	0.143	neutral	None	None	None	None	N
N/W	0.5265	ambiguous	0.4518	ambiguous	-0.694	Destabilizing	0.991	D	0.329	neutral	None	None	None	None	N
N/Y	0.1037	likely_benign	0.093	benign	-0.438	Destabilizing	0.014	N	0.159	neutral	N	0.413687061	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.