TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5257	15994;15995;15996	chr2:178733620;178733619;178733618	chr2:179598347;179598346;179598345
N2AB	4940	15043;15044;15045	chr2:178733620;178733619;178733618	chr2:179598347;179598346;179598345
N2A	4013	12262;12263;12264	chr2:178733620;178733619;178733618	chr2:179598347;179598346;179598345
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-35
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.2881
• 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/L	rs879227338	-0.273	0.618	D	0.721	0.666	0.32714864917	gnomAD-2.1.1	7.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
V/L	rs879227338	-0.273	0.618	D	0.721	0.666	0.32714864917	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/L	rs879227338	-0.273	0.618	D	0.721	0.666	0.32714864917	gnomAD-4.0.0	5.14754E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.63155E-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	0.6187	likely_pathogenic	0.6707	pathogenic	-1.439	Destabilizing	0.958	D	0.727	prob.delet.	D	0.768521078	None	None	N
V/C	0.9219	likely_pathogenic	0.9244	pathogenic	-1.075	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/D	0.9862	likely_pathogenic	0.9894	pathogenic	-0.91	Destabilizing	0.998	D	0.866	deleterious	D	0.767794125	None	None	N
V/E	0.949	likely_pathogenic	0.9582	pathogenic	-0.856	Destabilizing	0.998	D	0.862	deleterious	None	None	None	None	N
V/F	0.6506	likely_pathogenic	0.673	pathogenic	-0.897	Destabilizing	0.988	D	0.865	deleterious	D	0.70970468	None	None	N
V/G	0.7843	likely_pathogenic	0.8038	pathogenic	-1.81	Destabilizing	0.994	D	0.852	deleterious	D	0.767794125	None	None	N
V/H	0.9841	likely_pathogenic	0.9874	pathogenic	-1.339	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/I	0.0826	likely_benign	0.091	benign	-0.504	Destabilizing	0.067	N	0.545	neutral	D	0.561328652	None	None	N
V/K	0.9644	likely_pathogenic	0.9714	pathogenic	-1.123	Destabilizing	0.995	D	0.861	deleterious	None	None	None	None	N
V/L	0.4373	ambiguous	0.4583	ambiguous	-0.504	Destabilizing	0.618	D	0.721	prob.delet.	D	0.675127638	None	None	N
V/M	0.4623	ambiguous	0.5015	ambiguous	-0.533	Destabilizing	0.991	D	0.869	deleterious	None	None	None	None	N
V/N	0.9459	likely_pathogenic	0.9556	pathogenic	-0.99	Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
V/P	0.8747	likely_pathogenic	0.908	pathogenic	-0.781	Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
V/Q	0.9361	likely_pathogenic	0.9465	pathogenic	-1.053	Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
V/R	0.9413	likely_pathogenic	0.9503	pathogenic	-0.78	Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
V/S	0.823	likely_pathogenic	0.8461	pathogenic	-1.635	Destabilizing	0.995	D	0.854	deleterious	None	None	None	None	N
V/T	0.6817	likely_pathogenic	0.7223	pathogenic	-1.458	Destabilizing	0.968	D	0.812	deleterious	None	None	None	None	N
V/W	0.9843	likely_pathogenic	0.9876	pathogenic	-1.116	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/Y	0.9556	likely_pathogenic	0.9601	pathogenic	-0.798	Destabilizing	0.995	D	0.862	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.