TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8965	27118;27119;27120	chr2:178713241;178713240;178713239	chr2:179577968;179577967;179577966
N2AB	8648	26167;26168;26169	chr2:178713241;178713240;178713239	chr2:179577968;179577967;179577966
N2A	7721	23386;23387;23388	chr2:178713241;178713240;178713239	chr2:179577968;179577967;179577966
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-75
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4152
• 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
E/K	rs200325324	0.467	0.805	N	0.543	0.199	None	gnomAD-2.1.1	7.17E-05	None	None	None	None	N	None	1.2444E-04	0	None	0	0	None	1.31631E-04	None	1.60179E-04	6.27E-05	1.41044E-04
E/K	rs200325324	0.467	0.805	N	0.543	0.199	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	4.41E-05	2.07555E-04	0
E/K	rs200325324	0.467	0.805	N	0.543	0.199	None	gnomAD-4.0.0	4.83579E-05	None	None	None	None	N	None	2.67137E-05	0	None	0	0	None	2.50063E-04	0	3.5609E-05	1.75956E-04	3.2039E-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
E/A	0.1425	likely_benign	0.1687	benign	-0.536	Destabilizing	0.025	N	0.328	neutral	N	0.497426818	None	None	N
E/C	0.8153	likely_pathogenic	0.8832	pathogenic	-0.283	Destabilizing	0.997	D	0.716	prob.delet.	None	None	None	None	N
E/D	0.2418	likely_benign	0.2849	benign	-0.429	Destabilizing	0.892	D	0.515	neutral	N	0.506256945	None	None	N
E/F	0.721	likely_pathogenic	0.8091	pathogenic	-0.104	Destabilizing	0.987	D	0.707	prob.neutral	None	None	None	None	N
E/G	0.2012	likely_benign	0.2609	benign	-0.772	Destabilizing	0.805	D	0.555	neutral	D	0.523960058	None	None	N
E/H	0.4157	ambiguous	0.4809	ambiguous	0.24	Stabilizing	0.997	D	0.563	neutral	None	None	None	None	N
E/I	0.2802	likely_benign	0.3611	ambiguous	0.072	Stabilizing	0.975	D	0.713	prob.delet.	None	None	None	None	N
E/K	0.0763	likely_benign	0.0888	benign	0.279	Stabilizing	0.805	D	0.543	neutral	N	0.479955778	None	None	N
E/L	0.3149	likely_benign	0.3933	ambiguous	0.072	Stabilizing	0.95	D	0.585	neutral	None	None	None	None	N
E/M	0.3409	ambiguous	0.4113	ambiguous	0.085	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/N	0.3205	likely_benign	0.4181	ambiguous	-0.331	Destabilizing	0.987	D	0.534	neutral	None	None	None	None	N
E/P	0.3102	likely_benign	0.369	ambiguous	-0.111	Destabilizing	0.987	D	0.628	neutral	None	None	None	None	N
E/Q	0.1094	likely_benign	0.1186	benign	-0.249	Destabilizing	0.426	N	0.316	neutral	N	0.481630646	None	None	N
E/R	0.1459	likely_benign	0.1625	benign	0.615	Stabilizing	0.975	D	0.529	neutral	None	None	None	None	N
E/S	0.2392	likely_benign	0.303	benign	-0.464	Destabilizing	0.845	D	0.525	neutral	None	None	None	None	N
E/T	0.2185	likely_benign	0.2821	benign	-0.254	Destabilizing	0.916	D	0.549	neutral	None	None	None	None	N
E/V	0.1772	likely_benign	0.2223	benign	-0.111	Destabilizing	0.935	D	0.535	neutral	N	0.471723084	None	None	N
E/W	0.8734	likely_pathogenic	0.9244	pathogenic	0.167	Stabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.5889	likely_pathogenic	0.6906	pathogenic	0.173	Stabilizing	0.996	D	0.684	prob.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.