TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6956	21091;21092;21093	chr2:178724509;178724508;178724507	chr2:179589236;179589235;179589234
N2AB	6639	20140;20141;20142	chr2:178724509;178724508;178724507	chr2:179589236;179589235;179589234
N2A	5712	17359;17360;17361	chr2:178724509;178724508;178724507	chr2:179589236;179589235;179589234
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: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Ig-54
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5684
• 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
P/L	rs1054912076	0.118	0.426	N	0.404	0.157	0.442977140156	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
P/L	rs1054912076	0.118	0.426	N	0.404	0.157	0.442977140156	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs1054912076	0.118	0.426	N	0.404	0.157	0.442977140156	gnomAD-4.0.0	1.87337E-06	None	None	None	None	N	None	0	0	None	0	2.24507E-05	None	0	0	1.70738E-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
P/A	0.0657	likely_benign	0.0628	benign	-0.306	Destabilizing	0.012	N	0.243	neutral	N	0.47793054	None	None	N
P/C	0.4087	ambiguous	0.3286	benign	-0.688	Destabilizing	0.824	D	0.403	neutral	None	None	None	None	N
P/D	0.2382	likely_benign	0.2037	benign	-0.328	Destabilizing	0.035	N	0.251	neutral	None	None	None	None	N
P/E	0.1865	likely_benign	0.1712	benign	-0.45	Destabilizing	0.035	N	0.267	neutral	None	None	None	None	N
P/F	0.3236	likely_benign	0.2806	benign	-0.64	Destabilizing	0.555	D	0.422	neutral	None	None	None	None	N
P/G	0.2073	likely_benign	0.1695	benign	-0.393	Destabilizing	0.035	N	0.319	neutral	None	None	None	None	N
P/H	0.1291	likely_benign	0.1228	benign	-0.011	Destabilizing	0.555	D	0.391	neutral	None	None	None	None	N
P/I	0.2451	likely_benign	0.2371	benign	-0.227	Destabilizing	0.38	N	0.465	neutral	None	None	None	None	N
P/K	0.1796	likely_benign	0.177	benign	-0.376	Destabilizing	0.035	N	0.263	neutral	None	None	None	None	N
P/L	0.1065	likely_benign	0.1069	benign	-0.227	Destabilizing	0.426	N	0.404	neutral	N	0.482952358	None	None	N
P/M	0.242	likely_benign	0.2265	benign	-0.423	Destabilizing	0.791	D	0.379	neutral	None	None	None	None	N
P/N	0.1766	likely_benign	0.1457	benign	-0.144	Destabilizing	None	N	0.2	neutral	None	None	None	None	N
P/Q	0.1061	likely_benign	0.1043	benign	-0.382	Destabilizing	0.251	N	0.387	neutral	N	0.467233544	None	None	N
P/R	0.1241	likely_benign	0.1221	benign	0.105	Stabilizing	0.251	N	0.411	neutral	N	0.471908645	None	None	N
P/S	0.0805	likely_benign	0.0703	benign	-0.452	Destabilizing	None	N	0.107	neutral	N	0.423325264	None	None	N
P/T	0.079	likely_benign	0.0769	benign	-0.479	Destabilizing	0.027	N	0.281	neutral	N	0.453264169	None	None	N
P/V	0.1802	likely_benign	0.1694	benign	-0.221	Destabilizing	0.149	N	0.38	neutral	None	None	None	None	N
P/W	0.4747	ambiguous	0.4096	ambiguous	-0.716	Destabilizing	0.935	D	0.49	neutral	None	None	None	None	N
P/Y	0.3058	likely_benign	0.2612	benign	-0.418	Destabilizing	0.555	D	0.423	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.