TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29628	89107;89108;89109	chr2:178554465;178554464;178554463	chr2:179419192;179419191;179419190
N2AB	27987	84184;84185;84186	chr2:178554465;178554464;178554463	chr2:179419192;179419191;179419190
N2A	27060	81403;81404;81405	chr2:178554465;178554464;178554463	chr2:179419192;179419191;179419190
N2B	20563	61912;61913;61914	chr2:178554465;178554464;178554463	chr2:179419192;179419191;179419190
Novex-1	20688	62287;62288;62289	chr2:178554465;178554464;178554463	chr2:179419192;179419191;179419190
Novex-2	20755	62488;62489;62490	chr2:178554465;178554464;178554463	chr2:179419192;179419191;179419190
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-103
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.6238
• 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
K/R	rs1366016395	0.146	0.005	N	0.303	0.049	0.101711395817	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
K/R	rs1366016395	0.146	0.005	N	0.303	0.049	0.101711395817	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs1366016395	0.146	0.005	N	0.303	0.049	0.101711395817	gnomAD-4.0.0	3.71933E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08646E-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
K/A	0.4493	ambiguous	0.4116	ambiguous	-0.139	Destabilizing	0.46	N	0.603	neutral	None	None	None	None	N
K/C	0.5879	likely_pathogenic	0.5727	pathogenic	-0.221	Destabilizing	0.986	D	0.868	deleterious	None	None	None	None	N
K/D	0.7819	likely_pathogenic	0.7514	pathogenic	0.162	Stabilizing	0.749	D	0.735	deleterious	None	None	None	None	N
K/E	0.2366	likely_benign	0.2112	benign	0.181	Stabilizing	0.244	N	0.515	neutral	N	0.507203015	None	None	N
K/F	0.8664	likely_pathogenic	0.8599	pathogenic	-0.289	Destabilizing	0.958	D	0.819	deleterious	None	None	None	None	N
K/G	0.5904	likely_pathogenic	0.5495	ambiguous	-0.377	Destabilizing	0.749	D	0.623	neutral	None	None	None	None	N
K/H	0.3731	ambiguous	0.3408	ambiguous	-0.762	Destabilizing	0.958	D	0.717	prob.delet.	None	None	None	None	N
K/I	0.458	ambiguous	0.4231	ambiguous	0.415	Stabilizing	0.858	D	0.85	deleterious	None	None	None	None	N
K/L	0.5006	ambiguous	0.4665	ambiguous	0.415	Stabilizing	0.749	D	0.623	neutral	None	None	None	None	N
K/M	0.3307	likely_benign	0.3098	benign	0.344	Stabilizing	0.981	D	0.723	deleterious	N	0.474732465	None	None	N
K/N	0.6215	likely_pathogenic	0.5872	pathogenic	0.17	Stabilizing	0.693	D	0.671	prob.neutral	N	0.497698565	None	None	N
K/P	0.9684	likely_pathogenic	0.9673	pathogenic	0.26	Stabilizing	0.858	D	0.736	deleterious	None	None	None	None	N
K/Q	0.1263	likely_benign	0.1162	benign	-0.036	Destabilizing	0.693	D	0.692	prob.delet.	N	0.478322903	None	None	N
K/R	0.0733	likely_benign	0.0719	benign	-0.122	Destabilizing	0.005	N	0.303	neutral	N	0.457830201	None	None	N
K/S	0.5329	ambiguous	0.4953	ambiguous	-0.407	Destabilizing	0.46	N	0.631	neutral	None	None	None	None	N
K/T	0.2387	likely_benign	0.2096	benign	-0.224	Destabilizing	0.693	D	0.704	prob.delet.	N	0.517993225	None	None	N
K/V	0.3332	likely_benign	0.3083	benign	0.26	Stabilizing	0.749	D	0.783	deleterious	None	None	None	None	N
K/W	0.8221	likely_pathogenic	0.8054	pathogenic	-0.232	Destabilizing	0.986	D	0.874	deleterious	None	None	None	None	N
K/Y	0.762	likely_pathogenic	0.7443	pathogenic	0.116	Stabilizing	0.858	D	0.809	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.