TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24062	72409;72410;72411	chr2:178573948;178573947;178573946	chr2:179438675;179438674;179438673
N2AB	22421	67486;67487;67488	chr2:178573948;178573947;178573946	chr2:179438675;179438674;179438673
N2A	21494	64705;64706;64707	chr2:178573948;178573947;178573946	chr2:179438675;179438674;179438673
N2B	14997	45214;45215;45216	chr2:178573948;178573947;178573946	chr2:179438675;179438674;179438673
Novex-1	15122	45589;45590;45591	chr2:178573948;178573947;178573946	chr2:179438675;179438674;179438673
Novex-2	15189	45790;45791;45792	chr2:178573948;178573947;178573946	chr2:179438675;179438674;179438673
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-131
• Domain position: 34
• Structural Position: 47
• Q(SASA): 0.4696
• 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/G	rs893332061	None	0.27	N	0.459	0.305	0.402471007487	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
E/G	rs893332061	None	0.27	N	0.459	0.305	0.402471007487	gnomAD-4.0.0	2.56352E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78819E-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
E/A	0.0921	likely_benign	0.1059	benign	-0.53	Destabilizing	0.139	N	0.346	neutral	N	0.500563124	None	None	N
E/C	0.6195	likely_pathogenic	0.627	pathogenic	-0.087	Destabilizing	0.981	D	0.515	neutral	None	None	None	None	N
E/D	0.1467	likely_benign	0.1576	benign	-0.709	Destabilizing	0.425	N	0.406	neutral	D	0.523170624	None	None	N
E/F	0.414	ambiguous	0.4691	ambiguous	-0.367	Destabilizing	0.893	D	0.569	neutral	None	None	None	None	N
E/G	0.143	likely_benign	0.1611	benign	-0.803	Destabilizing	0.27	N	0.459	neutral	N	0.497141675	None	None	N
E/H	0.2547	likely_benign	0.2669	benign	-0.547	Destabilizing	0.981	D	0.48	neutral	None	None	None	None	N
E/I	0.1278	likely_benign	0.143	benign	0.178	Stabilizing	0.329	N	0.457	neutral	None	None	None	None	N
E/K	0.106	likely_benign	0.115	benign	-0.014	Destabilizing	0.002	N	0.211	neutral	N	0.46448768	None	None	N
E/L	0.1831	likely_benign	0.2123	benign	0.178	Stabilizing	0.176	N	0.408	neutral	None	None	None	None	N
E/M	0.1963	likely_benign	0.235	benign	0.497	Stabilizing	0.944	D	0.527	neutral	None	None	None	None	N
E/N	0.1735	likely_benign	0.2019	benign	-0.349	Destabilizing	0.704	D	0.402	neutral	None	None	None	None	N
E/P	0.9363	likely_pathogenic	0.947	pathogenic	-0.036	Destabilizing	0.828	D	0.494	neutral	None	None	None	None	N
E/Q	0.0893	likely_benign	0.0931	benign	-0.286	Destabilizing	0.642	D	0.415	neutral	N	0.455310837	None	None	N
E/R	0.166	likely_benign	0.1808	benign	0.113	Stabilizing	0.543	D	0.417	neutral	None	None	None	None	N
E/S	0.117	likely_benign	0.137	benign	-0.558	Destabilizing	0.013	N	0.203	neutral	None	None	None	None	N
E/T	0.0903	likely_benign	0.1115	benign	-0.337	Destabilizing	0.004	N	0.245	neutral	None	None	None	None	N
E/V	0.0904	likely_benign	0.0996	benign	-0.036	Destabilizing	0.001	N	0.321	neutral	N	0.43509028	None	None	N
E/W	0.7393	likely_pathogenic	0.7643	pathogenic	-0.213	Destabilizing	0.995	D	0.529	neutral	None	None	None	None	N
E/Y	0.3687	ambiguous	0.3868	ambiguous	-0.126	Destabilizing	0.944	D	0.571	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.