TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5827	17704;17705;17706	chr2:178731186;178731185;178731184	chr2:179595913;179595912;179595911
N2AB	5510	16753;16754;16755	chr2:178731186;178731185;178731184	chr2:179595913;179595912;179595911
N2A	4583	13972;13973;13974	chr2:178731186;178731185;178731184	chr2:179595913;179595912;179595911
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-42
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.3024
• 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	rs753975878	-0.03	0.426	N	0.351	0.197	None	gnomAD-2.1.1	4.02E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.55E-05	None	4.66E-05	6.22E-05	0
E/K	rs753975878	-0.03	0.426	N	0.351	0.197	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	6.55E-05	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs753975878	-0.03	0.426	N	0.351	0.197	None	gnomAD-4.0.0	1.67386E-05	None	None	None	None	N	None	1.33651E-05	1.66828E-05	None	0	0	None	1.56309E-05	0	1.69576E-05	4.39445E-05	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	0.2139	likely_benign	0.1926	benign	-0.516	Destabilizing	0.117	N	0.349	neutral	N	0.512009481	None	None	N
E/C	0.8945	likely_pathogenic	0.8854	pathogenic	-0.194	Destabilizing	0.935	D	0.491	neutral	None	None	None	None	N
E/D	0.1089	likely_benign	0.1112	benign	-0.495	Destabilizing	None	N	0.097	neutral	N	0.452366532	None	None	N
E/F	0.875	likely_pathogenic	0.857	pathogenic	-0.299	Destabilizing	0.791	D	0.461	neutral	None	None	None	None	N
E/G	0.2145	likely_benign	0.2006	benign	-0.744	Destabilizing	0.117	N	0.379	neutral	N	0.517378016	None	None	N
E/H	0.5512	ambiguous	0.5033	ambiguous	-0.134	Destabilizing	0.555	D	0.383	neutral	None	None	None	None	N
E/I	0.5996	likely_pathogenic	0.5502	ambiguous	0.059	Stabilizing	0.38	N	0.467	neutral	None	None	None	None	N
E/K	0.1938	likely_benign	0.1742	benign	0.088	Stabilizing	0.426	N	0.351	neutral	N	0.458887073	None	None	N
E/L	0.5924	likely_pathogenic	0.5606	ambiguous	0.059	Stabilizing	0.149	N	0.409	neutral	None	None	None	None	N
E/M	0.6424	likely_pathogenic	0.6041	pathogenic	0.172	Stabilizing	0.935	D	0.455	neutral	None	None	None	None	N
E/N	0.2798	likely_benign	0.2601	benign	-0.27	Destabilizing	0.081	N	0.302	neutral	None	None	None	None	N
E/P	0.9328	likely_pathogenic	0.8984	pathogenic	-0.112	Destabilizing	0.555	D	0.4	neutral	None	None	None	None	N
E/Q	0.1913	likely_benign	0.1666	benign	-0.225	Destabilizing	0.251	N	0.377	neutral	N	0.484724093	None	None	N
E/R	0.3437	ambiguous	0.314	benign	0.35	Stabilizing	0.38	N	0.373	neutral	None	None	None	None	N
E/S	0.2327	likely_benign	0.2076	benign	-0.445	Destabilizing	0.081	N	0.311	neutral	None	None	None	None	N
E/T	0.3104	likely_benign	0.2645	benign	-0.263	Destabilizing	0.002	N	0.211	neutral	None	None	None	None	N
E/V	0.3527	ambiguous	0.316	benign	-0.112	Destabilizing	0.117	N	0.385	neutral	N	0.512529556	None	None	N
E/W	0.9247	likely_pathogenic	0.9148	pathogenic	-0.113	Destabilizing	0.935	D	0.565	neutral	None	None	None	None	N
E/Y	0.7194	likely_pathogenic	0.6985	pathogenic	-0.057	Destabilizing	0.791	D	0.454	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.