TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20797	62614;62615;62616	chr2:178589336;178589335;178589334	chr2:179454063;179454062;179454061
N2AB	19156	57691;57692;57693	chr2:178589336;178589335;178589334	chr2:179454063;179454062;179454061
N2A	18229	54910;54911;54912	chr2:178589336;178589335;178589334	chr2:179454063;179454062;179454061
N2B	11732	35419;35420;35421	chr2:178589336;178589335;178589334	chr2:179454063;179454062;179454061
Novex-1	11857	35794;35795;35796	chr2:178589336;178589335;178589334	chr2:179454063;179454062;179454061
Novex-2	11924	35995;35996;35997	chr2:178589336;178589335;178589334	chr2:179454063;179454062;179454061
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-122
• Domain position: 29
• Structural Position: 42
• Q(SASA): 0.343
• 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
P/L	None	None	1.0	D	0.755	0.604	0.828969124369	gnomAD-4.0.0	6.84547E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99818E-07	0	0
P/Q	None	None	1.0	D	0.775	0.707	0.682284130214	gnomAD-4.0.0	1.36909E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79964E-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
P/A	0.9737	likely_pathogenic	0.9739	pathogenic	-0.86	Destabilizing	1.0	D	0.712	prob.delet.	D	0.552403763	None	None	I
P/C	0.998	likely_pathogenic	0.9978	pathogenic	-0.53	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/D	0.9903	likely_pathogenic	0.991	pathogenic	-0.74	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/E	0.9941	likely_pathogenic	0.9943	pathogenic	-0.841	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
P/F	0.9987	likely_pathogenic	0.9988	pathogenic	-0.964	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
P/G	0.9848	likely_pathogenic	0.9819	pathogenic	-1.04	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
P/H	0.9919	likely_pathogenic	0.9905	pathogenic	-0.626	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
P/I	0.9871	likely_pathogenic	0.9896	pathogenic	-0.519	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/K	0.9951	likely_pathogenic	0.9944	pathogenic	-0.762	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
P/L	0.976	likely_pathogenic	0.9804	pathogenic	-0.519	Destabilizing	1.0	D	0.755	deleterious	D	0.645442306	None	None	I
P/M	0.9945	likely_pathogenic	0.9956	pathogenic	-0.368	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
P/N	0.9892	likely_pathogenic	0.9891	pathogenic	-0.389	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
P/Q	0.9931	likely_pathogenic	0.9922	pathogenic	-0.664	Destabilizing	1.0	D	0.775	deleterious	D	0.578901808	None	None	I
P/R	0.9884	likely_pathogenic	0.9857	pathogenic	-0.166	Destabilizing	1.0	D	0.78	deleterious	D	0.628787172	None	None	I
P/S	0.9919	likely_pathogenic	0.9912	pathogenic	-0.741	Destabilizing	1.0	D	0.748	deleterious	D	0.56687394	None	None	I
P/T	0.9796	likely_pathogenic	0.9801	pathogenic	-0.748	Destabilizing	1.0	D	0.741	deleterious	D	0.619500586	None	None	I
P/V	0.9746	likely_pathogenic	0.9784	pathogenic	-0.597	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
P/W	0.9993	likely_pathogenic	0.9992	pathogenic	-1.058	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
P/Y	0.9966	likely_pathogenic	0.9964	pathogenic	-0.786	Destabilizing	1.0	D	0.817	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.