TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7985	24178;24179;24180	chr2:178719437;178719436;178719435	chr2:179584164;179584163;179584162
N2AB	7668	23227;23228;23229	chr2:178719437;178719436;178719435	chr2:179584164;179584163;179584162
N2A	6741	20446;20447;20448	chr2:178719437;178719436;178719435	chr2:179584164;179584163;179584162
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-65
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1682
• 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
P/A	None	None	1.0	D	0.839	0.678	0.642681104822	gnomAD-4.0.0	1.59403E-06	None	None	None	None	N	None	0	2.28843E-05	None	0	0	None	0	0	0	0	0
P/L	rs746422101	-0.166	1.0	D	0.893	0.625	0.9156675434	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
P/L	rs746422101	-0.166	1.0	D	0.893	0.625	0.9156675434	gnomAD-4.0.0	2.05414E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70038E-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
P/A	0.666	likely_pathogenic	0.6017	pathogenic	-1.38	Destabilizing	1.0	D	0.839	deleterious	D	0.599832645	None	None	N
P/C	0.9807	likely_pathogenic	0.9828	pathogenic	-1.439	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/D	0.9992	likely_pathogenic	0.9992	pathogenic	-1.311	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
P/E	0.9964	likely_pathogenic	0.9964	pathogenic	-1.337	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/F	0.998	likely_pathogenic	0.9982	pathogenic	-1.42	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/G	0.9868	likely_pathogenic	0.9852	pathogenic	-1.627	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/H	0.9937	likely_pathogenic	0.9949	pathogenic	-1.134	Destabilizing	1.0	D	0.865	deleterious	D	0.653835928	None	None	N
P/I	0.9608	likely_pathogenic	0.9634	pathogenic	-0.812	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/K	0.9976	likely_pathogenic	0.9979	pathogenic	-0.972	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
P/L	0.8948	likely_pathogenic	0.893	pathogenic	-0.812	Destabilizing	1.0	D	0.893	deleterious	D	0.621363237	None	None	N
P/M	0.9873	likely_pathogenic	0.9891	pathogenic	-0.786	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
P/N	0.9976	likely_pathogenic	0.9976	pathogenic	-0.865	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/Q	0.9902	likely_pathogenic	0.991	pathogenic	-1.121	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/R	0.9906	likely_pathogenic	0.9906	pathogenic	-0.499	Destabilizing	1.0	D	0.899	deleterious	D	0.653835928	None	None	N
P/S	0.9476	likely_pathogenic	0.9436	pathogenic	-1.4	Destabilizing	1.0	D	0.907	deleterious	D	0.621161433	None	None	N
P/T	0.9231	likely_pathogenic	0.9268	pathogenic	-1.319	Destabilizing	1.0	D	0.907	deleterious	D	0.653634124	None	None	N
P/V	0.8817	likely_pathogenic	0.883	pathogenic	-0.969	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9997	pathogenic	-1.497	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/Y	0.9987	likely_pathogenic	0.9989	pathogenic	-1.159	Destabilizing	1.0	D	0.894	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.