TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8629	26110;26111;26112	chr2:178715529;178715528;178715527	chr2:179580256;179580255;179580254
N2AB	8312	25159;25160;25161	chr2:178715529;178715528;178715527	chr2:179580256;179580255;179580254
N2A	7385	22378;22379;22380	chr2:178715529;178715528;178715527	chr2:179580256;179580255;179580254
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-71
• Domain position: 81
• Structural Position: 164
• Q(SASA): 0.2568
• Predicted PPI site: I

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
G/S	rs2077356013	None	1.0	D	0.803	0.813	0.555237559564	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
G/S	rs2077356013	None	1.0	D	0.803	0.813	0.555237559564	gnomAD-4.0.0	6.57479E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.07211E-04	0
G/V	None	None	1.0	D	0.837	0.828	0.942225882153	gnomAD-4.0.0	1.59355E-06	None	None	None	None	I	None	0	0	None	0	2.77393E-05	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
G/A	0.7405	likely_pathogenic	0.6051	pathogenic	-0.308	Destabilizing	1.0	D	0.753	deleterious	D	0.623124139	None	None	I
G/C	0.9498	likely_pathogenic	0.8933	pathogenic	-0.877	Destabilizing	1.0	D	0.81	deleterious	D	0.656373687	None	None	I
G/D	0.9415	likely_pathogenic	0.8761	pathogenic	-0.843	Destabilizing	1.0	D	0.857	deleterious	D	0.638739891	None	None	I
G/E	0.9625	likely_pathogenic	0.9221	pathogenic	-1.023	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/F	0.9849	likely_pathogenic	0.9733	pathogenic	-1.134	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/H	0.9788	likely_pathogenic	0.9526	pathogenic	-0.491	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/I	0.9825	likely_pathogenic	0.9636	pathogenic	-0.543	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/K	0.9777	likely_pathogenic	0.9502	pathogenic	-0.827	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/L	0.9784	likely_pathogenic	0.9587	pathogenic	-0.543	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/M	0.9869	likely_pathogenic	0.9728	pathogenic	-0.508	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/N	0.9553	likely_pathogenic	0.8923	pathogenic	-0.467	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/P	0.9986	likely_pathogenic	0.9982	pathogenic	-0.435	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
G/Q	0.9628	likely_pathogenic	0.921	pathogenic	-0.806	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
G/R	0.9429	likely_pathogenic	0.8862	pathogenic	-0.309	Destabilizing	1.0	D	0.867	deleterious	D	0.617986156	None	None	I
G/S	0.6248	likely_pathogenic	0.4783	ambiguous	-0.552	Destabilizing	1.0	D	0.803	deleterious	D	0.606267201	None	None	I
G/T	0.9235	likely_pathogenic	0.8523	pathogenic	-0.676	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/V	0.9566	likely_pathogenic	0.9164	pathogenic	-0.435	Destabilizing	1.0	D	0.837	deleterious	D	0.655970078	None	None	I
G/W	0.9803	likely_pathogenic	0.9654	pathogenic	-1.248	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/Y	0.9786	likely_pathogenic	0.9559	pathogenic	-0.923	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I

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.