TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7598	23017;23018;23019	chr2:178721871;178721870;178721869	chr2:179586598;179586597;179586596
N2AB	7281	22066;22067;22068	chr2:178721871;178721870;178721869	chr2:179586598;179586597;179586596
N2A	6354	19285;19286;19287	chr2:178721871;178721870;178721869	chr2:179586598;179586597;179586596
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-60
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1399
• 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
C/S	rs1316768329	-2.287	1.0	N	0.817	0.451	0.68100823904	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
C/S	rs1316768329	-2.287	1.0	N	0.817	0.451	0.68100823904	gnomAD-4.0.0	1.59652E-06	None	None	None	None	N	None	0	2.29137E-05	None	0	0	None	0	0	0	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
C/A	0.5419	ambiguous	0.5554	ambiguous	-2.217	Highly Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
C/D	0.9466	likely_pathogenic	0.9389	pathogenic	-1.218	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
C/E	0.9837	likely_pathogenic	0.9817	pathogenic	-1.074	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
C/F	0.6746	likely_pathogenic	0.6752	pathogenic	-1.396	Destabilizing	1.0	D	0.925	deleterious	N	0.486453252	None	None	N
C/G	0.3996	ambiguous	0.413	ambiguous	-2.555	Highly Destabilizing	1.0	D	0.873	deleterious	N	0.520436964	None	None	N
C/H	0.9329	likely_pathogenic	0.9327	pathogenic	-2.488	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
C/I	0.813	likely_pathogenic	0.8491	pathogenic	-1.312	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
C/K	0.9923	likely_pathogenic	0.9917	pathogenic	-1.681	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
C/L	0.8304	likely_pathogenic	0.8509	pathogenic	-1.312	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
C/M	0.8887	likely_pathogenic	0.8973	pathogenic	0.006	Stabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
C/N	0.9061	likely_pathogenic	0.8986	pathogenic	-1.781	Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	N
C/P	0.9979	likely_pathogenic	0.9978	pathogenic	-1.591	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
C/Q	0.9573	likely_pathogenic	0.9553	pathogenic	-1.61	Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
C/R	0.9396	likely_pathogenic	0.9385	pathogenic	-1.537	Destabilizing	1.0	D	0.929	deleterious	N	0.511297405	None	None	N
C/S	0.409	ambiguous	0.43	ambiguous	-2.309	Highly Destabilizing	1.0	D	0.817	deleterious	N	0.431623113	None	None	N
C/T	0.5616	ambiguous	0.5914	pathogenic	-1.988	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
C/V	0.6575	likely_pathogenic	0.7042	pathogenic	-1.591	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
C/W	0.9403	likely_pathogenic	0.9314	pathogenic	-1.461	Destabilizing	1.0	D	0.907	deleterious	D	0.536579852	None	None	N
C/Y	0.8636	likely_pathogenic	0.8585	pathogenic	-1.488	Destabilizing	1.0	D	0.924	deleterious	N	0.486706741	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.