TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26578	79957;79958;79959	chr2:178566400;178566399;178566398	chr2:179431127;179431126;179431125
N2AB	24937	75034;75035;75036	chr2:178566400;178566399;178566398	chr2:179431127;179431126;179431125
N2A	24010	72253;72254;72255	chr2:178566400;178566399;178566398	chr2:179431127;179431126;179431125
N2B	17513	52762;52763;52764	chr2:178566400;178566399;178566398	chr2:179431127;179431126;179431125
Novex-1	17638	53137;53138;53139	chr2:178566400;178566399;178566398	chr2:179431127;179431126;179431125
Novex-2	17705	53338;53339;53340	chr2:178566400;178566399;178566398	chr2:179431127;179431126;179431125
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-81
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.237
• 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/R	rs1286290994	-0.746	0.976	N	0.643	0.321	0.266843984389	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
P/R	rs1286290994	-0.746	0.976	N	0.643	0.321	0.266843984389	gnomAD-4.0.0	3.18376E-06	None	None	None	None	N	None	0	2.28645E-05	None	0	2.77331E-05	None	0	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
P/A	0.0811	likely_benign	0.0776	benign	-0.347	Destabilizing	0.919	D	0.685	prob.delet.	N	0.483717575	None	None	N
P/C	0.4697	ambiguous	0.4353	ambiguous	-0.812	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
P/D	0.4649	ambiguous	0.4137	ambiguous	-0.114	Destabilizing	0.883	D	0.739	deleterious	None	None	None	None	N
P/E	0.3111	likely_benign	0.2748	benign	-0.225	Destabilizing	0.168	N	0.567	neutral	None	None	None	None	N
P/F	0.4012	ambiguous	0.3656	ambiguous	-0.658	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
P/G	0.3035	likely_benign	0.2887	benign	-0.422	Destabilizing	0.968	D	0.706	prob.delet.	None	None	None	None	N
P/H	0.2054	likely_benign	0.1943	benign	-0.047	Destabilizing	0.997	D	0.703	prob.delet.	N	0.482097574	None	None	N
P/I	0.2481	likely_benign	0.2388	benign	-0.295	Destabilizing	0.997	D	0.75	deleterious	None	None	None	None	N
P/K	0.3143	likely_benign	0.2954	benign	-0.344	Destabilizing	0.883	D	0.717	prob.delet.	None	None	None	None	N
P/L	0.105	likely_benign	0.0976	benign	-0.295	Destabilizing	0.976	D	0.691	prob.delet.	N	0.455418036	None	None	N
P/M	0.2521	likely_benign	0.242	benign	-0.517	Destabilizing	0.999	D	0.705	prob.delet.	None	None	None	None	N
P/N	0.3095	likely_benign	0.2857	benign	-0.191	Destabilizing	0.991	D	0.68	prob.neutral	None	None	None	None	N
P/Q	0.1656	likely_benign	0.1554	benign	-0.374	Destabilizing	0.37	N	0.55	neutral	None	None	None	None	N
P/R	0.2327	likely_benign	0.2155	benign	0.062	Stabilizing	0.976	D	0.643	neutral	N	0.481337105	None	None	N
P/S	0.1267	likely_benign	0.1164	benign	-0.531	Destabilizing	0.919	D	0.751	deleterious	N	0.472788506	None	None	N
P/T	0.0958	likely_benign	0.0913	benign	-0.543	Destabilizing	0.988	D	0.704	prob.delet.	N	0.492414416	None	None	N
P/V	0.1831	likely_benign	0.1775	benign	-0.283	Destabilizing	0.991	D	0.665	prob.neutral	None	None	None	None	N
P/W	0.5961	likely_pathogenic	0.5661	pathogenic	-0.726	Destabilizing	0.999	D	0.689	prob.delet.	None	None	None	None	N
P/Y	0.4268	ambiguous	0.4072	ambiguous	-0.443	Destabilizing	0.997	D	0.717	prob.delet.	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.