TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5987	18184;18185;18186	chr2:178730574;178730573;178730572	chr2:179595301;179595300;179595299
N2AB	5670	17233;17234;17235	chr2:178730574;178730573;178730572	chr2:179595301;179595300;179595299
N2A	4743	14452;14453;14454	chr2:178730574;178730573;178730572	chr2:179595301;179595300;179595299
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: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-43
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.1426
• 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
G/E	None	None	1.0	D	0.841	0.678	0.847656369879	gnomAD-4.0.0	1.59172E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-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
G/A	0.5354	ambiguous	0.5559	ambiguous	-0.848	Destabilizing	1.0	D	0.727	prob.delet.	D	0.554039078	None	None	N
G/C	0.9405	likely_pathogenic	0.9388	pathogenic	-1.066	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/D	0.9524	likely_pathogenic	0.9414	pathogenic	-1.645	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/E	0.9832	likely_pathogenic	0.9822	pathogenic	-1.68	Destabilizing	1.0	D	0.841	deleterious	D	0.658552455	None	None	N
G/F	0.9946	likely_pathogenic	0.9946	pathogenic	-1.211	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/H	0.9916	likely_pathogenic	0.991	pathogenic	-1.476	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
G/I	0.9941	likely_pathogenic	0.9936	pathogenic	-0.395	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/K	0.9896	likely_pathogenic	0.9898	pathogenic	-1.272	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/L	0.9887	likely_pathogenic	0.9886	pathogenic	-0.395	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/M	0.9916	likely_pathogenic	0.9913	pathogenic	-0.263	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
G/N	0.9685	likely_pathogenic	0.9627	pathogenic	-1.058	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/P	0.9994	likely_pathogenic	0.9993	pathogenic	-0.506	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/Q	0.9769	likely_pathogenic	0.9769	pathogenic	-1.24	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/R	0.9685	likely_pathogenic	0.9699	pathogenic	-0.965	Destabilizing	1.0	D	0.837	deleterious	D	0.658350651	None	None	N
G/S	0.6323	likely_pathogenic	0.604	pathogenic	-1.322	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/T	0.9607	likely_pathogenic	0.9553	pathogenic	-1.28	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
G/V	0.9826	likely_pathogenic	0.9817	pathogenic	-0.506	Destabilizing	1.0	D	0.825	deleterious	D	0.658552455	None	None	N
G/W	0.9942	likely_pathogenic	0.9936	pathogenic	-1.614	Destabilizing	1.0	D	0.773	deleterious	D	0.658754259	None	None	N
G/Y	0.9943	likely_pathogenic	0.994	pathogenic	-1.188	Destabilizing	1.0	D	0.786	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.