TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25233	75922;75923;75924	chr2:178570435;178570434;178570433	chr2:179435162;179435161;179435160
N2AB	23592	70999;71000;71001	chr2:178570435;178570434;178570433	chr2:179435162;179435161;179435160
N2A	22665	68218;68219;68220	chr2:178570435;178570434;178570433	chr2:179435162;179435161;179435160
N2B	16168	48727;48728;48729	chr2:178570435;178570434;178570433	chr2:179435162;179435161;179435160
Novex-1	16293	49102;49103;49104	chr2:178570435;178570434;178570433	chr2:179435162;179435161;179435160
Novex-2	16360	49303;49304;49305	chr2:178570435;178570434;178570433	chr2:179435162;179435161;179435160
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-71
• Domain position: 30
• Structural Position: 31
• Q(SASA): 0.3528
• 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/C	None	None	1.0	D	0.8	0.635	0.582356428975	gnomAD-4.0.0	1.59252E-06	None	None	None	None	I	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	0.9572	likely_pathogenic	0.9582	pathogenic	-0.527	Destabilizing	1.0	D	0.732	prob.delet.	D	0.529658022	None	None	I
G/C	0.9864	likely_pathogenic	0.9865	pathogenic	-0.87	Destabilizing	1.0	D	0.8	deleterious	D	0.553802665	None	None	I
G/D	0.9962	likely_pathogenic	0.9963	pathogenic	-0.604	Destabilizing	1.0	D	0.828	deleterious	D	0.532910025	None	None	I
G/E	0.9976	likely_pathogenic	0.9976	pathogenic	-0.739	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
G/F	0.9988	likely_pathogenic	0.9989	pathogenic	-1.143	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/H	0.9986	likely_pathogenic	0.9987	pathogenic	-0.916	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/I	0.9984	likely_pathogenic	0.9984	pathogenic	-0.477	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/K	0.9981	likely_pathogenic	0.9984	pathogenic	-0.914	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/L	0.9984	likely_pathogenic	0.9984	pathogenic	-0.477	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/M	0.9991	likely_pathogenic	0.9992	pathogenic	-0.392	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/N	0.9974	likely_pathogenic	0.9975	pathogenic	-0.503	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
G/P	0.9996	likely_pathogenic	0.9996	pathogenic	-0.457	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/Q	0.9979	likely_pathogenic	0.9981	pathogenic	-0.776	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/R	0.991	likely_pathogenic	0.9923	pathogenic	-0.525	Destabilizing	1.0	D	0.836	deleterious	N	0.508831516	None	None	I
G/S	0.9479	likely_pathogenic	0.9479	pathogenic	-0.732	Destabilizing	1.0	D	0.796	deleterious	N	0.511767577	None	None	I
G/T	0.9942	likely_pathogenic	0.9947	pathogenic	-0.79	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/V	0.9965	likely_pathogenic	0.9965	pathogenic	-0.457	Destabilizing	1.0	D	0.815	deleterious	D	0.52679764	None	None	I
G/W	0.9967	likely_pathogenic	0.9969	pathogenic	-1.328	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/Y	0.9981	likely_pathogenic	0.9984	pathogenic	-0.965	Destabilizing	1.0	D	0.795	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.