TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6439	19540;19541;19542	chr2:178728611;178728610;178728609	chr2:179593338;179593337;179593336
N2AB	6122	18589;18590;18591	chr2:178728611;178728610;178728609	chr2:179593338;179593337;179593336
N2A	5195	15808;15809;15810	chr2:178728611;178728610;178728609	chr2:179593338;179593337;179593336
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-48
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2817
• 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
V/M	rs727505289	-0.501	0.953	N	0.582	0.254	0.444305618086	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	1.1212E-04	None	0	None	0	1.78E-05	0
V/M	rs727505289	-0.501	0.953	N	0.582	0.254	0.444305618086	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/M	rs727505289	-0.501	0.953	N	0.582	0.254	0.444305618086	gnomAD-4.0.0	1.42585E-05	None	None	None	None	N	None	0	0	None	0	2.45733E-04	None	0	0	8.47785E-06	1.0982E-05	1.60226E-05

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
V/A	0.3165	likely_benign	0.2437	benign	-1.597	Destabilizing	0.296	N	0.531	neutral	N	0.489616349	None	None	N
V/C	0.8691	likely_pathogenic	0.8066	pathogenic	-1.264	Destabilizing	0.991	D	0.707	prob.neutral	None	None	None	None	N
V/D	0.6906	likely_pathogenic	0.5266	ambiguous	-1.588	Destabilizing	0.906	D	0.803	deleterious	None	None	None	None	N
V/E	0.4467	ambiguous	0.3165	benign	-1.563	Destabilizing	0.879	D	0.755	deleterious	N	0.480195373	None	None	N
V/F	0.2539	likely_benign	0.1917	benign	-1.274	Destabilizing	0.826	D	0.72	prob.delet.	None	None	None	None	N
V/G	0.5639	ambiguous	0.4179	ambiguous	-1.934	Destabilizing	0.879	D	0.767	deleterious	N	0.490630307	None	None	N
V/H	0.6537	likely_pathogenic	0.5175	ambiguous	-1.497	Destabilizing	0.991	D	0.772	deleterious	None	None	None	None	N
V/I	0.0727	likely_benign	0.0699	benign	-0.756	Destabilizing	0.002	N	0.204	neutral	None	None	None	None	N
V/K	0.3281	likely_benign	0.2357	benign	-1.218	Destabilizing	0.906	D	0.759	deleterious	None	None	None	None	N
V/L	0.3016	likely_benign	0.2468	benign	-0.756	Destabilizing	0.074	N	0.374	neutral	N	0.487959186	None	None	N
V/M	0.173	likely_benign	0.1362	benign	-0.677	Destabilizing	0.953	D	0.582	neutral	N	0.487769925	None	None	N
V/N	0.4921	ambiguous	0.3625	ambiguous	-1.115	Destabilizing	0.967	D	0.803	deleterious	None	None	None	None	N
V/P	0.9876	likely_pathogenic	0.9777	pathogenic	-1.003	Destabilizing	0.967	D	0.772	deleterious	None	None	None	None	N
V/Q	0.3977	ambiguous	0.3058	benign	-1.274	Destabilizing	0.967	D	0.766	deleterious	None	None	None	None	N
V/R	0.2911	likely_benign	0.2168	benign	-0.765	Destabilizing	0.906	D	0.799	deleterious	None	None	None	None	N
V/S	0.4173	ambiguous	0.3141	benign	-1.677	Destabilizing	0.906	D	0.684	prob.neutral	None	None	None	None	N
V/T	0.2026	likely_benign	0.171	benign	-1.539	Destabilizing	0.575	D	0.525	neutral	None	None	None	None	N
V/W	0.8986	likely_pathogenic	0.8221	pathogenic	-1.488	Destabilizing	0.991	D	0.741	deleterious	None	None	None	None	N
V/Y	0.6746	likely_pathogenic	0.5654	pathogenic	-1.164	Destabilizing	0.906	D	0.729	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.