TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8508	25747;25748;25749	chr2:178717212;178717211;178717210	chr2:179581939;179581938;179581937
N2AB	8191	24796;24797;24798	chr2:178717212;178717211;178717210	chr2:179581939;179581938;179581937
N2A	7264	22015;22016;22017	chr2:178717212;178717211;178717210	chr2:179581939;179581938;179581937
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-70
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.5497
• Predicted PPI site: I

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/D	None	None	None	N	0.186	0.048	0.0762999501168	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/G	rs2154298886	None	0.8	N	0.447	0.214	0.238096912614	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.92678E-04	None	0	0	0	0	0
E/G	rs2154298886	None	0.8	N	0.447	0.214	0.238096912614	gnomAD-4.0.0	2.5623E-06	None	None	None	None	I	None	0	0	None	0	2.42483E-05	None	0	0	2.39373E-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	0.1715	likely_benign	0.194	benign	-0.183	Destabilizing	0.546	D	0.431	neutral	N	0.478911975	None	None	I
E/C	0.8739	likely_pathogenic	0.8956	pathogenic	-0.143	Destabilizing	0.992	D	0.584	neutral	None	None	None	None	I
E/D	0.0976	likely_benign	0.0972	benign	-0.184	Destabilizing	None	N	0.186	neutral	N	0.397178813	None	None	I
E/F	0.8658	likely_pathogenic	0.8968	pathogenic	-0.202	Destabilizing	0.985	D	0.499	neutral	None	None	None	None	I
E/G	0.0959	likely_benign	0.1048	benign	-0.325	Destabilizing	0.8	D	0.447	neutral	N	0.432923396	None	None	I
E/H	0.4633	ambiguous	0.4982	ambiguous	0.298	Stabilizing	0.937	D	0.388	neutral	None	None	None	None	I
E/I	0.7146	likely_pathogenic	0.7759	pathogenic	0.138	Stabilizing	0.908	D	0.502	neutral	None	None	None	None	I
E/K	0.1649	likely_benign	0.191	benign	0.291	Stabilizing	0.69	D	0.411	neutral	N	0.46392388	None	None	I
E/L	0.5831	likely_pathogenic	0.6581	pathogenic	0.138	Stabilizing	0.908	D	0.49	neutral	None	None	None	None	I
E/M	0.6515	likely_pathogenic	0.7099	pathogenic	0.018	Stabilizing	0.953	D	0.491	neutral	None	None	None	None	I
E/N	0.1883	likely_benign	0.1944	benign	0.142	Stabilizing	0.009	N	0.221	neutral	None	None	None	None	I
E/P	0.6418	likely_pathogenic	0.6936	pathogenic	0.05	Stabilizing	0.593	D	0.389	neutral	None	None	None	None	I
E/Q	0.1386	likely_benign	0.1541	benign	0.153	Stabilizing	0.919	D	0.372	neutral	N	0.479258692	None	None	I
E/R	0.2645	likely_benign	0.3022	benign	0.547	Stabilizing	0.954	D	0.378	neutral	None	None	None	None	I
E/S	0.1891	likely_benign	0.2062	benign	-0.051	Destabilizing	0.614	D	0.397	neutral	None	None	None	None	I
E/T	0.3512	ambiguous	0.4006	ambiguous	0.062	Stabilizing	0.687	D	0.399	neutral	None	None	None	None	I
E/V	0.4972	ambiguous	0.5641	pathogenic	0.05	Stabilizing	0.84	D	0.437	neutral	N	0.454819968	None	None	I
E/W	0.9083	likely_pathogenic	0.9282	pathogenic	-0.129	Destabilizing	0.998	D	0.622	neutral	None	None	None	None	I
E/Y	0.687	likely_pathogenic	0.7277	pathogenic	0.021	Stabilizing	0.994	D	0.456	neutral	None	None	None	None	I

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.