TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2491	7696;7697;7698	chr2:178773585;178773584;178773583	chr2:179638312;179638311;179638310
N2AB	2491	7696;7697;7698	chr2:178773585;178773584;178773583	chr2:179638312;179638311;179638310
N2A	2491	7696;7697;7698	chr2:178773585;178773584;178773583	chr2:179638312;179638311;179638310
N2B	2445	7558;7559;7560	chr2:178773585;178773584;178773583	chr2:179638312;179638311;179638310
Novex-1	2445	7558;7559;7560	chr2:178773585;178773584;178773583	chr2:179638312;179638311;179638310
Novex-2	2445	7558;7559;7560	chr2:178773585;178773584;178773583	chr2:179638312;179638311;179638310
Novex-3	2491	7696;7697;7698	chr2:178773585;178773584;178773583	chr2:179638312;179638311;179638310

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-14
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1297
• 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/I	rs976008348	None	0.37	N	0.224	0.143	0.370051654043	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
V/I	rs976008348	None	0.37	N	0.224	0.143	0.370051654043	gnomAD-4.0.0	6.57315E-06	None	None	None	None	N	None	0	6.55308E-05	None	0	0	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
V/A	0.4647	ambiguous	0.4653	ambiguous	-1.979	Destabilizing	0.978	D	0.473	neutral	D	0.577583831	None	None	N
V/C	0.7335	likely_pathogenic	0.7255	pathogenic	-1.602	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
V/D	0.8149	likely_pathogenic	0.8229	pathogenic	-2.602	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
V/E	0.663	likely_pathogenic	0.6697	pathogenic	-2.518	Highly Destabilizing	0.999	D	0.754	deleterious	D	0.645462936	None	None	N
V/F	0.143	likely_benign	0.1419	benign	-1.377	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
V/G	0.5165	ambiguous	0.5221	ambiguous	-2.381	Highly Destabilizing	0.999	D	0.785	deleterious	D	0.603802779	None	None	N
V/H	0.7014	likely_pathogenic	0.6987	pathogenic	-2.002	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/I	0.0715	likely_benign	0.069	benign	-0.918	Destabilizing	0.37	N	0.224	neutral	N	0.459198961	None	None	N
V/K	0.5913	likely_pathogenic	0.5876	pathogenic	-1.738	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
V/L	0.2461	likely_benign	0.237	benign	-0.918	Destabilizing	0.9	D	0.44	neutral	N	0.50528349	None	None	N
V/M	0.1922	likely_benign	0.1866	benign	-0.849	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
V/N	0.5927	likely_pathogenic	0.5841	pathogenic	-1.773	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
V/P	0.9663	likely_pathogenic	0.9662	pathogenic	-1.242	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
V/Q	0.6017	likely_pathogenic	0.6007	pathogenic	-1.854	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
V/R	0.5374	ambiguous	0.5369	ambiguous	-1.277	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
V/S	0.5144	ambiguous	0.5087	ambiguous	-2.288	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
V/T	0.3534	ambiguous	0.3463	ambiguous	-2.094	Highly Destabilizing	0.992	D	0.539	neutral	None	None	None	None	N
V/W	0.7965	likely_pathogenic	0.7948	pathogenic	-1.743	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
V/Y	0.5006	ambiguous	0.4974	ambiguous	-1.441	Destabilizing	0.999	D	0.757	deleterious	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.