TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22218	66877;66878;66879	chr2:178581616;178581615;178581614	chr2:179446343;179446342;179446341
N2AB	20577	61954;61955;61956	chr2:178581616;178581615;178581614	chr2:179446343;179446342;179446341
N2A	19650	59173;59174;59175	chr2:178581616;178581615;178581614	chr2:179446343;179446342;179446341
N2B	13153	39682;39683;39684	chr2:178581616;178581615;178581614	chr2:179446343;179446342;179446341
Novex-1	13278	40057;40058;40059	chr2:178581616;178581615;178581614	chr2:179446343;179446342;179446341
Novex-2	13345	40258;40259;40260	chr2:178581616;178581615;178581614	chr2:179446343;179446342;179446341
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: Fn3-49
• Domain position: 63
• Structural Position: 92
• Q(SASA): 0.6754
• 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/D	rs1210761677	-0.32	None	N	0.223	0.083	0.0666544352282	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/D	rs1210761677	-0.32	None	N	0.223	0.083	0.0666544352282	gnomAD-4.0.0	7.96772E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72433E-06	0	9.09146E-05
E/V	rs2047762977	None	None	N	0.267	0.203	0.32980341726	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.42E-05	0	0	0	0
E/V	rs2047762977	None	None	N	0.267	0.203	0.32980341726	gnomAD-4.0.0	6.57739E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.41797E-05	0	0	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	0.2265	likely_benign	0.2264	benign	-0.998	Destabilizing	0.011	N	0.244	neutral	N	0.455027543	None	None	N
E/C	0.8129	likely_pathogenic	0.804	pathogenic	-0.357	Destabilizing	0.781	D	0.418	neutral	None	None	None	None	N
E/D	0.2987	likely_benign	0.2938	benign	-0.742	Destabilizing	None	N	0.223	neutral	N	0.497412883	None	None	N
E/F	0.8271	likely_pathogenic	0.8287	pathogenic	-0.514	Destabilizing	0.142	N	0.535	neutral	None	None	None	None	N
E/G	0.4945	ambiguous	0.4894	ambiguous	-1.295	Destabilizing	0.049	N	0.309	neutral	N	0.498453033	None	None	N
E/H	0.5555	ambiguous	0.5668	pathogenic	-0.54	Destabilizing	0.54	D	0.406	neutral	None	None	None	None	N
E/I	0.2201	likely_benign	0.2381	benign	-0.201	Destabilizing	0.033	N	0.279	neutral	None	None	None	None	N
E/K	0.2476	likely_benign	0.2673	benign	-0.096	Destabilizing	0.049	N	0.35	neutral	N	0.432785402	None	None	N
E/L	0.3372	likely_benign	0.3554	ambiguous	-0.201	Destabilizing	None	N	0.361	neutral	None	None	None	None	N
E/M	0.4037	ambiguous	0.4149	ambiguous	0.191	Stabilizing	0.367	N	0.485	neutral	None	None	None	None	N
E/N	0.3955	ambiguous	0.3732	ambiguous	-0.686	Destabilizing	0.001	N	0.211	neutral	None	None	None	None	N
E/P	0.7656	likely_pathogenic	0.758	pathogenic	-0.447	Destabilizing	0.251	N	0.443	neutral	None	None	None	None	N
E/Q	0.1689	likely_benign	0.177	benign	-0.592	Destabilizing	0.111	N	0.397	neutral	N	0.467610051	None	None	N
E/R	0.3789	ambiguous	0.3917	ambiguous	0.147	Stabilizing	0.142	N	0.358	neutral	None	None	None	None	N
E/S	0.314	likely_benign	0.3085	benign	-0.902	Destabilizing	0.033	N	0.259	neutral	None	None	None	None	N
E/T	0.1549	likely_benign	0.1493	benign	-0.638	Destabilizing	None	N	0.213	neutral	None	None	None	None	N
E/V	0.1286	likely_benign	0.1401	benign	-0.447	Destabilizing	None	N	0.267	neutral	N	0.404502722	None	None	N
E/W	0.9566	likely_pathogenic	0.9551	pathogenic	-0.17	Destabilizing	0.931	D	0.439	neutral	None	None	None	None	N
E/Y	0.7779	likely_pathogenic	0.7779	pathogenic	-0.223	Destabilizing	0.54	D	0.551	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.