TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9087	27484;27485;27486	chr2:178712766;178712765;178712764	chr2:179577493;179577492;179577491
N2AB	8770	26533;26534;26535	chr2:178712766;178712765;178712764	chr2:179577493;179577492;179577491
N2A	7843	23752;23753;23754	chr2:178712766;178712765;178712764	chr2:179577493;179577492;179577491
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-76
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2639
• 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	rs1444251270	-0.742	1.0	D	0.888	0.816	0.86052713887	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14784E-04	0	None	0	0	None	0	None	0	0	0
G/E	rs1444251270	-0.742	1.0	D	0.888	0.816	0.86052713887	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	0
G/R	None	None	1.0	D	0.879	0.823	0.896446140896	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.3389	likely_benign	0.3568	ambiguous	-0.475	Destabilizing	0.998	D	0.785	deleterious	D	0.581434506	None	None	N
G/C	0.6853	likely_pathogenic	0.7722	pathogenic	-0.396	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/D	0.5243	ambiguous	0.6652	pathogenic	-1.118	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
G/E	0.635	likely_pathogenic	0.7898	pathogenic	-1.033	Destabilizing	1.0	D	0.888	deleterious	D	0.661570595	None	None	N
G/F	0.9488	likely_pathogenic	0.9735	pathogenic	-0.592	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/H	0.8694	likely_pathogenic	0.928	pathogenic	-1.519	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
G/I	0.9242	likely_pathogenic	0.9618	pathogenic	0.373	Stabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/K	0.8376	likely_pathogenic	0.9226	pathogenic	-0.83	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
G/L	0.8788	likely_pathogenic	0.926	pathogenic	0.373	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/M	0.8995	likely_pathogenic	0.9372	pathogenic	0.341	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
G/N	0.7307	likely_pathogenic	0.8182	pathogenic	-0.721	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
G/P	0.9885	likely_pathogenic	0.9938	pathogenic	0.135	Stabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/Q	0.7218	likely_pathogenic	0.8237	pathogenic	-0.662	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
G/R	0.6563	likely_pathogenic	0.7978	pathogenic	-0.888	Destabilizing	1.0	D	0.879	deleterious	D	0.661368791	None	None	N
G/S	0.2182	likely_benign	0.2637	benign	-1.068	Destabilizing	0.993	D	0.717	prob.delet.	None	None	None	None	N
G/T	0.669	likely_pathogenic	0.7702	pathogenic	-0.874	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
G/V	0.8286	likely_pathogenic	0.8996	pathogenic	0.135	Stabilizing	1.0	D	0.853	deleterious	D	0.661570595	None	None	N
G/W	0.872	likely_pathogenic	0.931	pathogenic	-1.287	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/Y	0.9218	likely_pathogenic	0.9606	pathogenic	-0.671	Destabilizing	1.0	D	0.853	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.