TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5967	18124;18125;18126	chr2:178730634;178730633;178730632	chr2:179595361;179595360;179595359
N2AB	5650	17173;17174;17175	chr2:178730634;178730633;178730632	chr2:179595361;179595360;179595359
N2A	4723	14392;14393;14394	chr2:178730634;178730633;178730632	chr2:179595361;179595360;179595359
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-43
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2354
• 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
F/L	rs1404382323	-0.186	0.139	N	0.256	0.175	0.340273420219	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
F/L	rs1404382323	-0.186	0.139	N	0.256	0.175	0.340273420219	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/L	rs1404382323	-0.186	0.139	N	0.256	0.175	0.340273420219	gnomAD-4.0.0	1.85932E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54307E-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
F/A	0.6127	likely_pathogenic	0.5825	pathogenic	-2.167	Highly Destabilizing	0.495	N	0.333	neutral	None	None	None	None	N
F/C	0.2502	likely_benign	0.2631	benign	-1.281	Destabilizing	0.001	N	0.275	neutral	N	0.46402632	None	None	N
F/D	0.8651	likely_pathogenic	0.8666	pathogenic	-0.931	Destabilizing	0.981	D	0.591	neutral	None	None	None	None	N
F/E	0.8756	likely_pathogenic	0.8772	pathogenic	-0.803	Destabilizing	0.828	D	0.591	neutral	None	None	None	None	N
F/G	0.8027	likely_pathogenic	0.8025	pathogenic	-2.543	Highly Destabilizing	0.828	D	0.492	neutral	None	None	None	None	N
F/H	0.5996	likely_pathogenic	0.6118	pathogenic	-0.827	Destabilizing	0.893	D	0.486	neutral	None	None	None	None	N
F/I	0.1648	likely_benign	0.1522	benign	-1.017	Destabilizing	0.642	D	0.354	neutral	N	0.361453739	None	None	N
F/K	0.8453	likely_pathogenic	0.8558	pathogenic	-1.305	Destabilizing	0.828	D	0.563	neutral	None	None	None	None	N
F/L	0.7708	likely_pathogenic	0.7781	pathogenic	-1.017	Destabilizing	0.139	N	0.256	neutral	N	0.417712454	None	None	N
F/M	0.4248	ambiguous	0.4057	ambiguous	-0.827	Destabilizing	0.981	D	0.449	neutral	None	None	None	None	N
F/N	0.646	likely_pathogenic	0.6513	pathogenic	-1.438	Destabilizing	0.944	D	0.581	neutral	None	None	None	None	N
F/P	0.9712	likely_pathogenic	0.9742	pathogenic	-1.397	Destabilizing	0.981	D	0.551	neutral	None	None	None	None	N
F/Q	0.7909	likely_pathogenic	0.7935	pathogenic	-1.432	Destabilizing	0.981	D	0.542	neutral	None	None	None	None	N
F/R	0.7767	likely_pathogenic	0.7748	pathogenic	-0.773	Destabilizing	0.944	D	0.578	neutral	None	None	None	None	N
F/S	0.4995	ambiguous	0.4731	ambiguous	-2.275	Highly Destabilizing	0.784	D	0.441	neutral	N	0.451385097	None	None	N
F/T	0.5151	ambiguous	0.4749	ambiguous	-2.045	Highly Destabilizing	0.828	D	0.444	neutral	None	None	None	None	N
F/V	0.188	likely_benign	0.1706	benign	-1.397	Destabilizing	0.425	N	0.386	neutral	N	0.402201497	None	None	N
F/W	0.4721	ambiguous	0.5144	ambiguous	-0.072	Destabilizing	0.944	D	0.451	neutral	None	None	None	None	N
F/Y	0.0768	likely_benign	0.0938	benign	-0.355	Destabilizing	0.001	N	0.068	neutral	N	0.421582265	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.