TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27062	81409;81410;81411	chr2:178564948;178564947;178564946	chr2:179429675;179429674;179429673
N2AB	25421	76486;76487;76488	chr2:178564948;178564947;178564946	chr2:179429675;179429674;179429673
N2A	24494	73705;73706;73707	chr2:178564948;178564947;178564946	chr2:179429675;179429674;179429673
N2B	17997	54214;54215;54216	chr2:178564948;178564947;178564946	chr2:179429675;179429674;179429673
Novex-1	18122	54589;54590;54591	chr2:178564948;178564947;178564946	chr2:179429675;179429674;179429673
Novex-2	18189	54790;54791;54792	chr2:178564948;178564947;178564946	chr2:179429675;179429674;179429673
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: Fn3-84
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.1422
• 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/M	None	None	0.468	N	0.393	0.164	0.246773566709	gnomAD-4.0.0	6.8486E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99954E-07	0	0
K/R	rs1705141926	None	0.094	N	0.397	0.07	0.144782658237	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
K/R	rs1705141926	None	0.094	N	0.397	0.07	0.144782658237	gnomAD-4.0.0	6.57212E-06	None	None	None	None	N	None	0	6.54793E-05	None	0	0	None	0	0	0	0	0
K/T	None	None	0.001	N	0.24	0.147	0.181679512989	gnomAD-4.0.0	2.05458E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79991E-06	0	1.65887E-05

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	0.1546	likely_benign	0.1353	benign	-0.29	Destabilizing	0.029	N	0.359	neutral	None	None	None	None	N
K/C	0.495	ambiguous	0.4508	ambiguous	-0.508	Destabilizing	0.878	D	0.584	neutral	None	None	None	None	N
K/D	0.2284	likely_benign	0.2033	benign	0.041	Stabilizing	0.064	N	0.403	neutral	None	None	None	None	N
K/E	0.0879	likely_benign	0.0828	benign	0.121	Stabilizing	0.001	N	0.267	neutral	N	0.362861169	None	None	N
K/F	0.6367	likely_pathogenic	0.5699	pathogenic	-0.237	Destabilizing	0.538	D	0.631	neutral	None	None	None	None	N
K/G	0.255	likely_benign	0.2158	benign	-0.565	Destabilizing	0.064	N	0.491	neutral	None	None	None	None	N
K/H	0.2431	likely_benign	0.2198	benign	-0.692	Destabilizing	0.538	D	0.393	neutral	None	None	None	None	N
K/I	0.2472	likely_benign	0.2191	benign	0.387	Stabilizing	0.001	N	0.537	neutral	None	None	None	None	N
K/L	0.2355	likely_benign	0.2015	benign	0.387	Stabilizing	0.023	N	0.486	neutral	None	None	None	None	N
K/M	0.1875	likely_benign	0.1673	benign	-0.042	Destabilizing	0.468	N	0.393	neutral	N	0.510800681	None	None	N
K/N	0.206	likely_benign	0.1768	benign	-0.195	Destabilizing	None	N	0.219	neutral	N	0.450674942	None	None	N
K/P	0.2185	likely_benign	0.1794	benign	0.19	Stabilizing	None	N	0.227	neutral	None	None	None	None	N
K/Q	0.1043	likely_benign	0.0972	benign	-0.215	Destabilizing	0.201	N	0.415	neutral	N	0.4508483	None	None	N
K/R	0.0884	likely_benign	0.0859	benign	-0.203	Destabilizing	0.094	N	0.397	neutral	N	0.510453964	None	None	N
K/S	0.1965	likely_benign	0.1671	benign	-0.719	Destabilizing	0.001	N	0.184	neutral	None	None	None	None	N
K/T	0.1136	likely_benign	0.1015	benign	-0.453	Destabilizing	0.001	N	0.24	neutral	N	0.457504914	None	None	N
K/V	0.1878	likely_benign	0.1663	benign	0.19	Stabilizing	0.023	N	0.489	neutral	None	None	None	None	N
K/W	0.7377	likely_pathogenic	0.6939	pathogenic	-0.233	Destabilizing	0.964	D	0.653	prob.neutral	None	None	None	None	N
K/Y	0.5051	ambiguous	0.4633	ambiguous	0.088	Stabilizing	0.703	D	0.635	neutral	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.