TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6885	20878;20879;20880	chr2:178725551;178725550;178725549	chr2:179590278;179590277;179590276
N2AB	6568	19927;19928;19929	chr2:178725551;178725550;178725549	chr2:179590278;179590277;179590276
N2A	5641	17146;17147;17148	chr2:178725551;178725550;178725549	chr2:179590278;179590277;179590276
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-53
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2242
• 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	rs2079191317	None	0.543	N	0.285	0.266	0.63713380425	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs2079191317	None	0.543	N	0.285	0.266	0.63713380425	gnomAD-4.0.0	6.57609E-06	None	None	None	None	N	None	2.41394E-05	0	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	0.559	ambiguous	0.5515	ambiguous	-1.698	Destabilizing	0.994	D	0.663	neutral	D	0.61401792	None	None	N
V/C	0.8899	likely_pathogenic	0.8829	pathogenic	-1.054	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/D	0.974	likely_pathogenic	0.979	pathogenic	-1.861	Destabilizing	0.999	D	0.844	deleterious	D	0.615026942	None	None	N
V/E	0.9324	likely_pathogenic	0.9387	pathogenic	-1.715	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/F	0.4143	ambiguous	0.4311	ambiguous	-1.041	Destabilizing	0.997	D	0.756	deleterious	D	0.58154523	None	None	N
V/G	0.7501	likely_pathogenic	0.7672	pathogenic	-2.146	Highly Destabilizing	0.999	D	0.841	deleterious	D	0.615026942	None	None	N
V/H	0.9664	likely_pathogenic	0.9661	pathogenic	-1.719	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/I	0.0901	likely_benign	0.083	benign	-0.495	Destabilizing	0.543	D	0.285	neutral	N	0.505745231	None	None	N
V/K	0.939	likely_pathogenic	0.9422	pathogenic	-1.436	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/L	0.3653	ambiguous	0.3468	ambiguous	-0.495	Destabilizing	0.217	N	0.321	neutral	D	0.567131379	None	None	N
V/M	0.4046	ambiguous	0.3852	ambiguous	-0.42	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
V/N	0.939	likely_pathogenic	0.9376	pathogenic	-1.505	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/P	0.8855	likely_pathogenic	0.8863	pathogenic	-0.866	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/Q	0.9045	likely_pathogenic	0.9107	pathogenic	-1.463	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/R	0.9011	likely_pathogenic	0.9105	pathogenic	-1.159	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/S	0.7694	likely_pathogenic	0.7619	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/T	0.5857	likely_pathogenic	0.5457	ambiguous	-1.797	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
V/W	0.9631	likely_pathogenic	0.9616	pathogenic	-1.419	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/Y	0.8986	likely_pathogenic	0.9005	pathogenic	-1.039	Destabilizing	1.0	D	0.736	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.