TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5140	15643;15644;15645	chr2:178734406;178734405;178734404	chr2:179599133;179599132;179599131
N2AB	4823	14692;14693;14694	chr2:178734406;178734405;178734404	chr2:179599133;179599132;179599131
N2A	3896	11911;11912;11913	chr2:178734406;178734405;178734404	chr2:179599133;179599132;179599131
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-34
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.453
• 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
A/V	rs753106533	0.035	1.0	D	0.624	0.536	0.638815175438	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
A/V	rs753106533	0.035	1.0	D	0.624	0.536	0.638815175438	gnomAD-4.0.0	1.36865E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.32035E-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
A/C	0.6972	likely_pathogenic	0.6977	pathogenic	-0.755	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
A/D	0.76	likely_pathogenic	0.632	pathogenic	-0.138	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
A/E	0.7611	likely_pathogenic	0.6364	pathogenic	-0.279	Destabilizing	1.0	D	0.749	deleterious	N	0.493222884	None	None	N
A/F	0.6091	likely_pathogenic	0.5603	ambiguous	-0.803	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
A/G	0.1988	likely_benign	0.189	benign	-0.309	Destabilizing	1.0	D	0.571	neutral	N	0.512587608	None	None	N
A/H	0.7772	likely_pathogenic	0.7249	pathogenic	-0.254	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
A/I	0.3918	ambiguous	0.3778	ambiguous	-0.295	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
A/K	0.885	likely_pathogenic	0.8154	pathogenic	-0.497	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
A/L	0.2824	likely_benign	0.2638	benign	-0.295	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
A/M	0.3328	likely_benign	0.3232	benign	-0.385	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
A/N	0.3987	ambiguous	0.3528	ambiguous	-0.213	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
A/P	0.4719	ambiguous	0.4822	ambiguous	-0.248	Destabilizing	1.0	D	0.745	deleterious	D	0.629535952	None	None	N
A/Q	0.6279	likely_pathogenic	0.5776	pathogenic	-0.446	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
A/R	0.8445	likely_pathogenic	0.7559	pathogenic	-0.075	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
A/S	0.1151	likely_benign	0.1039	benign	-0.481	Destabilizing	1.0	D	0.554	neutral	N	0.434125916	None	None	N
A/T	0.1273	likely_benign	0.113	benign	-0.531	Destabilizing	1.0	D	0.681	prob.neutral	N	0.514436672	None	None	N
A/V	0.1925	likely_benign	0.1816	benign	-0.248	Destabilizing	1.0	D	0.624	neutral	D	0.589080381	None	None	N
A/W	0.9067	likely_pathogenic	0.8946	pathogenic	-0.938	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
A/Y	0.7643	likely_pathogenic	0.7355	pathogenic	-0.59	Destabilizing	1.0	D	0.777	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.