TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9271	28036;28037;28038	chr2:178712019;178712018;178712017	chr2:179576746;179576745;179576744
N2AB	8954	27085;27086;27087	chr2:178712019;178712018;178712017	chr2:179576746;179576745;179576744
N2A	8027	24304;24305;24306	chr2:178712019;178712018;178712017	chr2:179576746;179576745;179576744
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-78
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1722
• 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
D/N	None	None	1.0	D	0.775	0.742	0.711529652176	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
D/A	0.8162	likely_pathogenic	0.9121	pathogenic	0.977	Stabilizing	1.0	D	0.84	deleterious	D	0.624602824	None	None	N
D/C	0.9601	likely_pathogenic	0.982	pathogenic	0.747	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
D/E	0.7819	likely_pathogenic	0.8702	pathogenic	-0.376	Destabilizing	1.0	D	0.581	neutral	D	0.613873247	None	None	N
D/F	0.9586	likely_pathogenic	0.9855	pathogenic	1.634	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
D/G	0.8617	likely_pathogenic	0.9376	pathogenic	0.49	Stabilizing	1.0	D	0.772	deleterious	D	0.666362101	None	None	N
D/H	0.7592	likely_pathogenic	0.8888	pathogenic	1.263	Stabilizing	1.0	D	0.833	deleterious	D	0.599468321	None	None	N
D/I	0.9399	likely_pathogenic	0.9762	pathogenic	2.285	Highly Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
D/K	0.9555	likely_pathogenic	0.9828	pathogenic	0.802	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/L	0.9483	likely_pathogenic	0.9792	pathogenic	2.285	Highly Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
D/M	0.9737	likely_pathogenic	0.99	pathogenic	2.548	Highly Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
D/N	0.4416	ambiguous	0.5914	pathogenic	-0.122	Destabilizing	1.0	D	0.775	deleterious	D	0.61950592	None	None	N
D/P	0.9955	likely_pathogenic	0.9983	pathogenic	1.881	Stabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
D/Q	0.9208	likely_pathogenic	0.9676	pathogenic	0.285	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
D/R	0.9639	likely_pathogenic	0.987	pathogenic	0.639	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
D/S	0.6102	likely_pathogenic	0.7586	pathogenic	-0.396	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/T	0.8622	likely_pathogenic	0.9348	pathogenic	0.074	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
D/V	0.8652	likely_pathogenic	0.9362	pathogenic	1.881	Stabilizing	1.0	D	0.843	deleterious	D	0.666765709	None	None	N
D/W	0.9945	likely_pathogenic	0.998	pathogenic	1.587	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
D/Y	0.8081	likely_pathogenic	0.9093	pathogenic	1.931	Stabilizing	1.0	D	0.849	deleterious	D	0.650544544	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.