TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26569	79930;79931;79932	chr2:178566427;178566426;178566425	chr2:179431154;179431153;179431152
N2AB	24928	75007;75008;75009	chr2:178566427;178566426;178566425	chr2:179431154;179431153;179431152
N2A	24001	72226;72227;72228	chr2:178566427;178566426;178566425	chr2:179431154;179431153;179431152
N2B	17504	52735;52736;52737	chr2:178566427;178566426;178566425	chr2:179431154;179431153;179431152
Novex-1	17629	53110;53111;53112	chr2:178566427;178566426;178566425	chr2:179431154;179431153;179431152
Novex-2	17696	53311;53312;53313	chr2:178566427;178566426;178566425	chr2:179431154;179431153;179431152
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-81
• Domain position: 83
• Structural Position: 114
• Q(SASA): 0.5574
• 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
V/L	None	None	None	N	0.123	0.12	0.170165803431	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	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
V/A	0.0751	likely_benign	0.0847	benign	-0.508	Destabilizing	0.001	N	0.141	neutral	N	0.391149423	None	None	I
V/C	0.6015	likely_pathogenic	0.6105	pathogenic	-0.731	Destabilizing	0.836	D	0.481	neutral	None	None	None	None	I
V/D	0.4355	ambiguous	0.4384	ambiguous	-0.376	Destabilizing	0.794	D	0.582	neutral	N	0.46584860299999997	None	None	I
V/E	0.2847	likely_benign	0.2772	benign	-0.498	Destabilizing	0.418	N	0.557	neutral	None	None	None	None	I
V/F	0.1738	likely_benign	0.1627	benign	-0.751	Destabilizing	0.351	N	0.475	neutral	N	0.510651539	None	None	I
V/G	0.1959	likely_benign	0.2031	benign	-0.615	Destabilizing	0.213	N	0.555	neutral	N	0.497988886	None	None	I
V/H	0.5527	ambiguous	0.5286	ambiguous	-0.084	Destabilizing	0.983	D	0.567	neutral	None	None	None	None	I
V/I	0.0836	likely_benign	0.0812	benign	-0.378	Destabilizing	0.001	N	0.124	neutral	N	0.447928212	None	None	I
V/K	0.4537	ambiguous	0.4142	ambiguous	-0.467	Destabilizing	0.418	N	0.579	neutral	None	None	None	None	I
V/L	0.1954	likely_benign	0.1994	benign	-0.378	Destabilizing	None	N	0.123	neutral	N	0.466764689	None	None	I
V/M	0.1341	likely_benign	0.1317	benign	-0.449	Destabilizing	0.022	N	0.236	neutral	None	None	None	None	I
V/N	0.2768	likely_benign	0.2783	benign	-0.256	Destabilizing	0.836	D	0.595	neutral	None	None	None	None	I
V/P	0.7404	likely_pathogenic	0.7817	pathogenic	-0.388	Destabilizing	0.836	D	0.572	neutral	None	None	None	None	I
V/Q	0.3258	likely_benign	0.3261	benign	-0.52	Destabilizing	0.836	D	0.585	neutral	None	None	None	None	I
V/R	0.3826	ambiguous	0.36	ambiguous	0.107	Stabilizing	0.716	D	0.582	neutral	None	None	None	None	I
V/S	0.1472	likely_benign	0.1581	benign	-0.604	Destabilizing	0.264	N	0.503	neutral	None	None	None	None	I
V/T	0.1361	likely_benign	0.1371	benign	-0.628	Destabilizing	0.228	N	0.269	neutral	None	None	None	None	I
V/W	0.7801	likely_pathogenic	0.7673	pathogenic	-0.794	Destabilizing	0.983	D	0.567	neutral	None	None	None	None	I
V/Y	0.4896	ambiguous	0.4831	ambiguous	-0.515	Destabilizing	0.836	D	0.489	neutral	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.