TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29657	89194;89195;89196	chr2:178554142;178554141;178554140	chr2:179418869;179418868;179418867
N2AB	28016	84271;84272;84273	chr2:178554142;178554141;178554140	chr2:179418869;179418868;179418867
N2A	27089	81490;81491;81492	chr2:178554142;178554141;178554140	chr2:179418869;179418868;179418867
N2B	20592	61999;62000;62001	chr2:178554142;178554141;178554140	chr2:179418869;179418868;179418867
Novex-1	20717	62374;62375;62376	chr2:178554142;178554141;178554140	chr2:179418869;179418868;179418867
Novex-2	20784	62575;62576;62577	chr2:178554142;178554141;178554140	chr2:179418869;179418868;179418867
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-104
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1438
• 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/T	rs1700388515	None	1.0	D	0.847	0.669	0.610467662648	gnomAD-4.0.0	6.84252E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99471E-07	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	0.9058	likely_pathogenic	0.9468	pathogenic	-1.694	Destabilizing	1.0	D	0.827	deleterious	D	0.576721569	None	None	N
P/C	0.9912	likely_pathogenic	0.9946	pathogenic	-1.134	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/D	0.9968	likely_pathogenic	0.998	pathogenic	-1.592	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/E	0.9949	likely_pathogenic	0.9968	pathogenic	-1.547	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/F	0.9993	likely_pathogenic	0.9996	pathogenic	-1.212	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/G	0.98	likely_pathogenic	0.9885	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/H	0.9937	likely_pathogenic	0.9963	pathogenic	-1.652	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/I	0.9935	likely_pathogenic	0.9963	pathogenic	-0.737	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/K	0.9977	likely_pathogenic	0.9986	pathogenic	-1.513	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/L	0.9716	likely_pathogenic	0.9831	pathogenic	-0.737	Destabilizing	1.0	D	0.921	deleterious	D	0.632966136	None	None	N
P/M	0.9954	likely_pathogenic	0.9976	pathogenic	-0.571	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/N	0.9943	likely_pathogenic	0.9968	pathogenic	-1.332	Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
P/Q	0.9923	likely_pathogenic	0.9956	pathogenic	-1.43	Destabilizing	1.0	D	0.845	deleterious	D	0.633975157	None	None	N
P/R	0.9931	likely_pathogenic	0.9956	pathogenic	-1.041	Destabilizing	1.0	D	0.911	deleterious	D	0.624486767	None	None	N
P/S	0.9662	likely_pathogenic	0.9833	pathogenic	-1.876	Destabilizing	1.0	D	0.848	deleterious	D	0.565870551	None	None	N
P/T	0.9679	likely_pathogenic	0.984	pathogenic	-1.71	Destabilizing	1.0	D	0.847	deleterious	D	0.601532826	None	None	N
P/V	0.9809	likely_pathogenic	0.9888	pathogenic	-1.022	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9998	pathogenic	-1.462	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/Y	0.9992	likely_pathogenic	0.9995	pathogenic	-1.171	Destabilizing	1.0	D	0.916	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.