TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6934	21025;21026;21027	chr2:178725404;178725403;178725402	chr2:179590131;179590130;179590129
N2AB	6617	20074;20075;20076	chr2:178725404;178725403;178725402	chr2:179590131;179590130;179590129
N2A	5690	17293;17294;17295	chr2:178725404;178725403;178725402	chr2:179590131;179590130;179590129
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-53
• Domain position: 81
• Structural Position: 164
• Q(SASA): 0.3028
• 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/R	rs2079167703	None	1.0	D	0.881	0.686	0.875557798454	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/R	rs2079167703	None	1.0	D	0.881	0.686	0.875557798454	gnomAD-4.0.0	5.20927E-06	None	None	None	None	I	None	1.69635E-05	0	None	0	0	None	0	0	7.30048E-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
G/A	0.6209	likely_pathogenic	0.6731	pathogenic	-0.458	Destabilizing	1.0	D	0.747	deleterious	D	0.596657369	None	None	I
G/C	0.8122	likely_pathogenic	0.8597	pathogenic	-0.854	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
G/D	0.8514	likely_pathogenic	0.8879	pathogenic	-1.144	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
G/E	0.8671	likely_pathogenic	0.9019	pathogenic	-1.314	Destabilizing	1.0	D	0.848	deleterious	D	0.548476515	None	None	I
G/F	0.9469	likely_pathogenic	0.9584	pathogenic	-1.196	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/H	0.9412	likely_pathogenic	0.9592	pathogenic	-0.775	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/I	0.9089	likely_pathogenic	0.9365	pathogenic	-0.577	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/K	0.9477	likely_pathogenic	0.9623	pathogenic	-1.122	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
G/L	0.9411	likely_pathogenic	0.9578	pathogenic	-0.577	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/M	0.9471	likely_pathogenic	0.9623	pathogenic	-0.475	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/N	0.871	likely_pathogenic	0.904	pathogenic	-0.678	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/P	0.9949	likely_pathogenic	0.9967	pathogenic	-0.504	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
G/Q	0.8863	likely_pathogenic	0.9231	pathogenic	-1.03	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
G/R	0.8694	likely_pathogenic	0.907	pathogenic	-0.564	Destabilizing	1.0	D	0.881	deleterious	D	0.622397285	None	None	I
G/S	0.4305	ambiguous	0.5192	ambiguous	-0.74	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/T	0.7875	likely_pathogenic	0.8523	pathogenic	-0.861	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
G/V	0.8546	likely_pathogenic	0.8972	pathogenic	-0.504	Destabilizing	1.0	D	0.848	deleterious	D	0.623002697	None	None	I
G/W	0.9151	likely_pathogenic	0.9364	pathogenic	-1.348	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/Y	0.9201	likely_pathogenic	0.9339	pathogenic	-1.029	Destabilizing	1.0	D	0.851	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.