TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30828	92707;92708;92709	chr2:178549144;178549143;178549142	chr2:179413871;179413870;179413869
N2AB	29187	87784;87785;87786	chr2:178549144;178549143;178549142	chr2:179413871;179413870;179413869
N2A	28260	85003;85004;85005	chr2:178549144;178549143;178549142	chr2:179413871;179413870;179413869
N2B	21763	65512;65513;65514	chr2:178549144;178549143;178549142	chr2:179413871;179413870;179413869
Novex-1	21888	65887;65888;65889	chr2:178549144;178549143;178549142	chr2:179413871;179413870;179413869
Novex-2	21955	66088;66089;66090	chr2:178549144;178549143;178549142	chr2:179413871;179413870;179413869
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: Fn3-113
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2292
• 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	0.565	N	0.696	0.245	0.57371630461	gnomAD-4.0.0	1.59119E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85793E-06	0	0
V/I	rs754257799	-0.355	0.034	N	0.248	0.109	0.396494342077	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	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	0.3456	ambiguous	0.3448	ambiguous	-2.084	Highly Destabilizing	0.565	D	0.696	prob.neutral	N	0.459553502	None	None	N
V/C	0.7992	likely_pathogenic	0.8099	pathogenic	-1.741	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
V/D	0.9591	likely_pathogenic	0.9563	pathogenic	-3.088	Highly Destabilizing	0.901	D	0.825	deleterious	N	0.47721227	None	None	N
V/E	0.9131	likely_pathogenic	0.9078	pathogenic	-2.865	Highly Destabilizing	0.923	D	0.806	deleterious	None	None	None	None	N
V/F	0.3967	ambiguous	0.4056	ambiguous	-1.126	Destabilizing	0.949	D	0.758	deleterious	N	0.484179801	None	None	N
V/G	0.523	ambiguous	0.5347	ambiguous	-2.61	Highly Destabilizing	0.901	D	0.803	deleterious	N	0.489329044	None	None	N
V/H	0.9656	likely_pathogenic	0.9645	pathogenic	-2.5	Highly Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
V/I	0.0851	likely_benign	0.0866	benign	-0.605	Destabilizing	0.034	N	0.248	neutral	N	0.42871052	None	None	N
V/K	0.938	likely_pathogenic	0.9326	pathogenic	-1.809	Destabilizing	0.923	D	0.809	deleterious	None	None	None	None	N
V/L	0.2089	likely_benign	0.2209	benign	-0.605	Destabilizing	0.349	N	0.689	prob.neutral	N	0.359263504	None	None	N
V/M	0.2521	likely_benign	0.261	benign	-0.799	Destabilizing	0.961	D	0.668	neutral	None	None	None	None	N
V/N	0.8809	likely_pathogenic	0.8736	pathogenic	-2.176	Highly Destabilizing	0.961	D	0.83	deleterious	None	None	None	None	N
V/P	0.4777	ambiguous	0.4458	ambiguous	-1.074	Destabilizing	0.024	N	0.579	neutral	None	None	None	None	N
V/Q	0.8942	likely_pathogenic	0.8904	pathogenic	-1.991	Destabilizing	0.961	D	0.801	deleterious	None	None	None	None	N
V/R	0.9152	likely_pathogenic	0.9089	pathogenic	-1.677	Destabilizing	0.961	D	0.83	deleterious	None	None	None	None	N
V/S	0.6715	likely_pathogenic	0.6656	pathogenic	-2.698	Highly Destabilizing	0.923	D	0.777	deleterious	None	None	None	None	N
V/T	0.5257	ambiguous	0.5161	ambiguous	-2.345	Highly Destabilizing	0.775	D	0.725	prob.delet.	None	None	None	None	N
V/W	0.9655	likely_pathogenic	0.967	pathogenic	-1.759	Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	N
V/Y	0.9008	likely_pathogenic	0.9041	pathogenic	-1.389	Destabilizing	0.987	D	0.732	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.