TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5254	15985;15986;15987	chr2:178733629;178733628;178733627	chr2:179598356;179598355;179598354
N2AB	4937	15034;15035;15036	chr2:178733629;178733628;178733627	chr2:179598356;179598355;179598354
N2A	4010	12253;12254;12255	chr2:178733629;178733628;178733627	chr2:179598356;179598355;179598354
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-35
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.5722
• 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/K	rs867275748	None	0.016	N	0.187	0.259	0.245660935333	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs867275748	None	0.016	N	0.187	0.259	0.245660935333	gnomAD-4.0.0	6.57125E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46994E-05	0	0
E/Q	rs867275748	-0.128	0.549	N	0.564	0.241	0.321672782286	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/Q	rs867275748	-0.128	0.549	N	0.564	0.241	0.321672782286	gnomAD-4.0.0	1.59662E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87137E-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	0.1544	likely_benign	0.1884	benign	-0.823	Destabilizing	0.201	N	0.504	neutral	N	0.489532373	None	None	I
E/C	0.7767	likely_pathogenic	0.8424	pathogenic	-0.292	Destabilizing	0.992	D	0.588	neutral	None	None	None	None	I
E/D	0.1205	likely_benign	0.1513	benign	-0.687	Destabilizing	0.004	N	0.154	neutral	N	0.502620239	None	None	I
E/F	0.5876	likely_pathogenic	0.6562	pathogenic	-0.428	Destabilizing	0.972	D	0.615	neutral	None	None	None	None	I
E/G	0.1961	likely_benign	0.2336	benign	-1.118	Destabilizing	0.549	D	0.587	neutral	N	0.517101612	None	None	I
E/H	0.3217	likely_benign	0.4053	ambiguous	-0.561	Destabilizing	0.972	D	0.609	neutral	None	None	None	None	I
E/I	0.2594	likely_benign	0.3361	benign	-0.039	Destabilizing	0.85	D	0.623	neutral	None	None	None	None	I
E/K	0.1198	likely_benign	0.1516	benign	-0.12	Destabilizing	0.016	N	0.187	neutral	N	0.462378486	None	None	I
E/L	0.3042	likely_benign	0.3837	ambiguous	-0.039	Destabilizing	0.617	D	0.605	neutral	None	None	None	None	I
E/M	0.3435	ambiguous	0.4104	ambiguous	0.302	Stabilizing	0.992	D	0.591	neutral	None	None	None	None	I
E/N	0.1666	likely_benign	0.202	benign	-0.572	Destabilizing	0.447	N	0.568	neutral	None	None	None	None	I
E/P	0.8289	likely_pathogenic	0.8818	pathogenic	-0.279	Destabilizing	0.766	D	0.645	neutral	None	None	None	None	I
E/Q	0.1149	likely_benign	0.1312	benign	-0.495	Destabilizing	0.549	D	0.564	neutral	N	0.479002908	None	None	I
E/R	0.2185	likely_benign	0.2666	benign	0.079	Stabilizing	0.447	N	0.592	neutral	None	None	None	None	I
E/S	0.163	likely_benign	0.1894	benign	-0.814	Destabilizing	0.059	N	0.196	neutral	None	None	None	None	I
E/T	0.1624	likely_benign	0.1953	benign	-0.565	Destabilizing	0.009	N	0.23	neutral	None	None	None	None	I
E/V	0.1649	likely_benign	0.2072	benign	-0.279	Destabilizing	0.549	D	0.593	neutral	N	0.470530415	None	None	I
E/W	0.8212	likely_pathogenic	0.8761	pathogenic	-0.154	Destabilizing	0.992	D	0.61	neutral	None	None	None	None	I
E/Y	0.4393	ambiguous	0.5201	ambiguous	-0.158	Destabilizing	0.972	D	0.611	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.