TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20705	62338;62339;62340	chr2:178589612;178589611;178589610	chr2:179454339;179454338;179454337
N2AB	19064	57415;57416;57417	chr2:178589612;178589611;178589610	chr2:179454339;179454338;179454337
N2A	18137	54634;54635;54636	chr2:178589612;178589611;178589610	chr2:179454339;179454338;179454337
N2B	11640	35143;35144;35145	chr2:178589612;178589611;178589610	chr2:179454339;179454338;179454337
Novex-1	11765	35518;35519;35520	chr2:178589612;178589611;178589610	chr2:179454339;179454338;179454337
Novex-2	11832	35719;35720;35721	chr2:178589612;178589611;178589610	chr2:179454339;179454338;179454337
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: Fn3-38
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0916
• 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	rs1318869377	None	0.134	N	0.226	0.162	0.452450644169	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	rs1318869377	None	0.134	N	0.226	0.162	0.452450644169	gnomAD-4.0.0	2.56411E-06	None	None	None	None	N	None	1.69233E-05	0	None	0	0	None	0	0	2.39499E-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	0.9209	likely_pathogenic	0.9255	pathogenic	-2.587	Highly Destabilizing	0.906	D	0.576	neutral	D	0.528145945	None	None	N
V/C	0.9788	likely_pathogenic	0.9777	pathogenic	-1.999	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
V/D	0.9995	likely_pathogenic	0.9993	pathogenic	-3.02	Highly Destabilizing	0.996	D	0.863	deleterious	D	0.528906413	None	None	N
V/E	0.9976	likely_pathogenic	0.9966	pathogenic	-2.774	Highly Destabilizing	0.997	D	0.807	deleterious	None	None	None	None	N
V/F	0.9424	likely_pathogenic	0.9357	pathogenic	-1.463	Destabilizing	0.976	D	0.711	prob.delet.	D	0.528652924	None	None	N
V/G	0.9781	likely_pathogenic	0.9736	pathogenic	-3.019	Highly Destabilizing	0.996	D	0.815	deleterious	D	0.528906413	None	None	N
V/H	0.9994	likely_pathogenic	0.9992	pathogenic	-2.568	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
V/I	0.0988	likely_benign	0.1113	benign	-1.289	Destabilizing	0.134	N	0.226	neutral	N	0.461535015	None	None	N
V/K	0.9979	likely_pathogenic	0.9971	pathogenic	-2.208	Highly Destabilizing	0.997	D	0.779	deleterious	None	None	None	None	N
V/L	0.5785	likely_pathogenic	0.5719	pathogenic	-1.289	Destabilizing	0.005	N	0.299	neutral	N	0.472698945	None	None	N
V/M	0.7927	likely_pathogenic	0.8142	pathogenic	-1.668	Destabilizing	0.982	D	0.599	neutral	None	None	None	None	N
V/N	0.9986	likely_pathogenic	0.9981	pathogenic	-2.815	Highly Destabilizing	0.997	D	0.871	deleterious	None	None	None	None	N
V/P	0.9981	likely_pathogenic	0.9968	pathogenic	-1.716	Destabilizing	0.997	D	0.835	deleterious	None	None	None	None	N
V/Q	0.9975	likely_pathogenic	0.9964	pathogenic	-2.515	Highly Destabilizing	0.997	D	0.85	deleterious	None	None	None	None	N
V/R	0.9958	likely_pathogenic	0.9934	pathogenic	-2.224	Highly Destabilizing	0.997	D	0.865	deleterious	None	None	None	None	N
V/S	0.9918	likely_pathogenic	0.9903	pathogenic	-3.14	Highly Destabilizing	0.997	D	0.771	deleterious	None	None	None	None	N
V/T	0.9346	likely_pathogenic	0.9375	pathogenic	-2.781	Highly Destabilizing	0.969	D	0.567	neutral	None	None	None	None	N
V/W	0.9991	likely_pathogenic	0.9992	pathogenic	-1.64	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/Y	0.9971	likely_pathogenic	0.9966	pathogenic	-1.661	Destabilizing	0.997	D	0.745	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.