TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26744	80455;80456;80457	chr2:178565902;178565901;178565900	chr2:179430629;179430628;179430627
N2AB	25103	75532;75533;75534	chr2:178565902;178565901;178565900	chr2:179430629;179430628;179430627
N2A	24176	72751;72752;72753	chr2:178565902;178565901;178565900	chr2:179430629;179430628;179430627
N2B	17679	53260;53261;53262	chr2:178565902;178565901;178565900	chr2:179430629;179430628;179430627
Novex-1	17804	53635;53636;53637	chr2:178565902;178565901;178565900	chr2:179430629;179430628;179430627
Novex-2	17871	53836;53837;53838	chr2:178565902;178565901;178565900	chr2:179430629;179430628;179430627
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-82
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.1121
• 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	0.097	N	0.355	0.429	0.524584940466	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4312	ambiguous	0.461	ambiguous	-1.755	Destabilizing	0.097	N	0.355	neutral	N	0.493470101	None	None	N
V/C	0.9179	likely_pathogenic	0.9246	pathogenic	-1.255	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
V/D	0.9916	likely_pathogenic	0.9922	pathogenic	-2.444	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/E	0.9726	likely_pathogenic	0.9736	pathogenic	-2.165	Highly Destabilizing	0.999	D	0.821	deleterious	D	0.545909988	None	None	N
V/F	0.7063	likely_pathogenic	0.6981	pathogenic	-1.025	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
V/G	0.8367	likely_pathogenic	0.8481	pathogenic	-2.335	Highly Destabilizing	0.995	D	0.81	deleterious	D	0.545909988	None	None	N
V/H	0.9926	likely_pathogenic	0.9925	pathogenic	-2.213	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/I	0.0914	likely_benign	0.0937	benign	-0.112	Destabilizing	0.015	N	0.267	neutral	None	None	None	None	N
V/K	0.9883	likely_pathogenic	0.9874	pathogenic	-1.441	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/L	0.4703	ambiguous	0.4696	ambiguous	-0.112	Destabilizing	0.738	D	0.615	neutral	N	0.519460237	None	None	N
V/M	0.4515	ambiguous	0.4644	ambiguous	-0.228	Destabilizing	0.999	D	0.708	prob.delet.	D	0.522525814	None	None	N
V/N	0.975	likely_pathogenic	0.9776	pathogenic	-1.941	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
V/P	0.9633	likely_pathogenic	0.9711	pathogenic	-0.635	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
V/Q	0.9736	likely_pathogenic	0.9765	pathogenic	-1.658	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/R	0.9801	likely_pathogenic	0.9796	pathogenic	-1.532	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/S	0.8709	likely_pathogenic	0.8895	pathogenic	-2.537	Highly Destabilizing	0.988	D	0.803	deleterious	None	None	None	None	N
V/T	0.6175	likely_pathogenic	0.6448	pathogenic	-2.091	Highly Destabilizing	0.948	D	0.671	neutral	None	None	None	None	N
V/W	0.9903	likely_pathogenic	0.9892	pathogenic	-1.579	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/Y	0.9652	likely_pathogenic	0.9645	pathogenic	-1.113	Destabilizing	0.999	D	0.755	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.