TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17759	53500;53501;53502	chr2:178607413;178607412;178607411	chr2:179472140;179472139;179472138
N2AB	16118	48577;48578;48579	chr2:178607413;178607412;178607411	chr2:179472140;179472139;179472138
N2A	15191	45796;45797;45798	chr2:178607413;178607412;178607411	chr2:179472140;179472139;179472138
N2B	8694	26305;26306;26307	chr2:178607413;178607412;178607411	chr2:179472140;179472139;179472138
Novex-1	8819	26680;26681;26682	chr2:178607413;178607412;178607411	chr2:179472140;179472139;179472138
Novex-2	8886	26881;26882;26883	chr2:178607413;178607412;178607411	chr2:179472140;179472139;179472138
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-113
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.1376
• 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	rs752508699	-0.671	0.863	N	0.611	0.187	0.229264304666	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/L	rs752508699	-0.671	0.863	N	0.611	0.187	0.229264304666	gnomAD-4.0.0	1.59268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43316E-05	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	0.8157	likely_pathogenic	0.7764	pathogenic	-2.342	Highly Destabilizing	0.046	N	0.337	neutral	N	0.505835186	None	None	N
V/C	0.9588	likely_pathogenic	0.9513	pathogenic	-1.8	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
V/D	0.9982	likely_pathogenic	0.9979	pathogenic	-3.173	Highly Destabilizing	0.993	D	0.841	deleterious	None	None	None	None	N
V/E	0.9949	likely_pathogenic	0.9943	pathogenic	-2.945	Highly Destabilizing	0.982	D	0.815	deleterious	D	0.52444642	None	None	N
V/F	0.916	likely_pathogenic	0.8763	pathogenic	-1.413	Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	N
V/G	0.9066	likely_pathogenic	0.8957	pathogenic	-2.884	Highly Destabilizing	0.964	D	0.789	deleterious	D	0.52444642	None	None	N
V/H	0.9989	likely_pathogenic	0.9986	pathogenic	-2.664	Highly Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
V/I	0.1604	likely_benign	0.1462	benign	-0.81	Destabilizing	0.863	D	0.553	neutral	N	0.461531919	None	None	N
V/K	0.9963	likely_pathogenic	0.9963	pathogenic	-2.065	Highly Destabilizing	0.986	D	0.814	deleterious	None	None	None	None	N
V/L	0.8043	likely_pathogenic	0.7672	pathogenic	-0.81	Destabilizing	0.863	D	0.611	neutral	N	0.46729418	None	None	N
V/M	0.8522	likely_pathogenic	0.8062	pathogenic	-0.786	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
V/N	0.9955	likely_pathogenic	0.9944	pathogenic	-2.424	Highly Destabilizing	0.993	D	0.83	deleterious	None	None	None	None	N
V/P	0.9933	likely_pathogenic	0.9921	pathogenic	-1.297	Destabilizing	0.993	D	0.822	deleterious	None	None	None	None	N
V/Q	0.9948	likely_pathogenic	0.9942	pathogenic	-2.258	Highly Destabilizing	0.993	D	0.811	deleterious	None	None	None	None	N
V/R	0.9925	likely_pathogenic	0.9921	pathogenic	-1.83	Destabilizing	0.993	D	0.821	deleterious	None	None	None	None	N
V/S	0.9761	likely_pathogenic	0.9697	pathogenic	-2.999	Highly Destabilizing	0.973	D	0.788	deleterious	None	None	None	None	N
V/T	0.8775	likely_pathogenic	0.8675	pathogenic	-2.636	Highly Destabilizing	0.953	D	0.606	neutral	None	None	None	None	N
V/W	0.9988	likely_pathogenic	0.9983	pathogenic	-2.015	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/Y	0.9947	likely_pathogenic	0.9926	pathogenic	-1.658	Destabilizing	0.998	D	0.773	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.