TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30838	92737;92738;92739	chr2:178549114;178549113;178549112	chr2:179413841;179413840;179413839
N2AB	29197	87814;87815;87816	chr2:178549114;178549113;178549112	chr2:179413841;179413840;179413839
N2A	28270	85033;85034;85035	chr2:178549114;178549113;178549112	chr2:179413841;179413840;179413839
N2B	21773	65542;65543;65544	chr2:178549114;178549113;178549112	chr2:179413841;179413840;179413839
Novex-1	21898	65917;65918;65919	chr2:178549114;178549113;178549112	chr2:179413841;179413840;179413839
Novex-2	21965	66118;66119;66120	chr2:178549114;178549113;178549112	chr2:179413841;179413840;179413839
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: Fn3-113
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1004
• 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/A	None	None	0.822	N	0.609	0.263	0.382592752248	gnomAD-4.0.0	6.84207E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99473E-07	0	0
V/G	None	None	0.971	N	0.868	0.511	0.835745670459	gnomAD-4.0.0	2.05265E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69845E-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
V/A	0.4225	ambiguous	0.3946	ambiguous	-2.301	Highly Destabilizing	0.822	D	0.609	neutral	N	0.487995605	None	None	N
V/C	0.8902	likely_pathogenic	0.8957	pathogenic	-2.876	Highly Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
V/D	0.9948	likely_pathogenic	0.9931	pathogenic	-2.748	Highly Destabilizing	0.993	D	0.867	deleterious	None	None	None	None	N
V/E	0.9869	likely_pathogenic	0.9843	pathogenic	-2.507	Highly Destabilizing	0.99	D	0.868	deleterious	D	0.532826984	None	None	N
V/F	0.7265	likely_pathogenic	0.7097	pathogenic	-1.622	Destabilizing	0.956	D	0.847	deleterious	None	None	None	None	N
V/G	0.8358	likely_pathogenic	0.8165	pathogenic	-2.839	Highly Destabilizing	0.971	D	0.868	deleterious	N	0.521470679	None	None	N
V/H	0.9947	likely_pathogenic	0.994	pathogenic	-2.555	Highly Destabilizing	0.998	D	0.861	deleterious	None	None	None	None	N
V/I	0.0866	likely_benign	0.0862	benign	-0.777	Destabilizing	0.019	N	0.205	neutral	None	None	None	None	N
V/K	0.9926	likely_pathogenic	0.9911	pathogenic	-1.937	Destabilizing	0.978	D	0.869	deleterious	None	None	None	None	N
V/L	0.4971	ambiguous	0.4705	ambiguous	-0.777	Destabilizing	0.247	N	0.485	neutral	N	0.456225546	None	None	N
V/M	0.4611	ambiguous	0.4518	ambiguous	-1.379	Destabilizing	0.942	D	0.749	deleterious	N	0.485235715	None	None	N
V/N	0.9766	likely_pathogenic	0.9735	pathogenic	-2.393	Highly Destabilizing	0.993	D	0.887	deleterious	None	None	None	None	N
V/P	0.9955	likely_pathogenic	0.9944	pathogenic	-1.262	Destabilizing	0.993	D	0.87	deleterious	None	None	None	None	N
V/Q	0.983	likely_pathogenic	0.9809	pathogenic	-2.201	Highly Destabilizing	0.993	D	0.878	deleterious	None	None	None	None	N
V/R	0.9832	likely_pathogenic	0.9806	pathogenic	-1.847	Destabilizing	0.993	D	0.887	deleterious	None	None	None	None	N
V/S	0.8421	likely_pathogenic	0.8343	pathogenic	-3.117	Highly Destabilizing	0.978	D	0.861	deleterious	None	None	None	None	N
V/T	0.7346	likely_pathogenic	0.7153	pathogenic	-2.709	Highly Destabilizing	0.86	D	0.703	prob.neutral	None	None	None	None	N
V/W	0.9963	likely_pathogenic	0.9963	pathogenic	-1.94	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
V/Y	0.9747	likely_pathogenic	0.9729	pathogenic	-1.636	Destabilizing	0.978	D	0.84	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.