TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8290	25093;25094;25095	chr2:178718138;178718137;178718136	chr2:179582865;179582864;179582863
N2AB	7973	24142;24143;24144	chr2:178718138;178718137;178718136	chr2:179582865;179582864;179582863
N2A	7046	21361;21362;21363	chr2:178718138;178718137;178718136	chr2:179582865;179582864;179582863
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-68
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5419
• 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
T/N	None	None	0.969	N	0.464	0.274	0.521015664611	gnomAD-4.0.0	1.6026E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43303E-05	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
T/A	0.1515	likely_benign	0.1478	benign	-0.171	Destabilizing	0.004	N	0.2	neutral	N	0.493423721	None	None	I
T/C	0.7054	likely_pathogenic	0.7121	pathogenic	-0.354	Destabilizing	1.0	D	0.581	neutral	None	None	None	None	I
T/D	0.5764	likely_pathogenic	0.6053	pathogenic	0.128	Stabilizing	0.976	D	0.499	neutral	None	None	None	None	I
T/E	0.4601	ambiguous	0.4918	ambiguous	0.058	Stabilizing	0.975	D	0.523	neutral	None	None	None	None	I
T/F	0.2864	likely_benign	0.2946	benign	-0.693	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
T/G	0.5129	ambiguous	0.5107	ambiguous	-0.285	Destabilizing	0.98	D	0.605	neutral	None	None	None	None	I
T/H	0.3279	likely_benign	0.3262	benign	-0.42	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
T/I	0.2536	likely_benign	0.2766	benign	0.008	Stabilizing	0.993	D	0.525	neutral	N	0.510433401	None	None	I
T/K	0.2214	likely_benign	0.2358	benign	-0.321	Destabilizing	0.982	D	0.521	neutral	None	None	None	None	I
T/L	0.1589	likely_benign	0.1768	benign	0.008	Stabilizing	0.982	D	0.513	neutral	None	None	None	None	I
T/M	0.1157	likely_benign	0.1179	benign	-0.103	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	I
T/N	0.1662	likely_benign	0.1816	benign	-0.154	Destabilizing	0.969	D	0.464	neutral	N	0.475107319	None	None	I
T/P	0.4896	ambiguous	0.523	ambiguous	-0.024	Destabilizing	0.984	D	0.551	neutral	N	0.511269457	None	None	I
T/Q	0.292	likely_benign	0.3015	benign	-0.332	Destabilizing	0.994	D	0.555	neutral	None	None	None	None	I
T/R	0.2105	likely_benign	0.216	benign	-0.015	Destabilizing	0.998	D	0.559	neutral	None	None	None	None	I
T/S	0.142	likely_benign	0.1378	benign	-0.333	Destabilizing	0.037	N	0.192	neutral	N	0.435607568	None	None	I
T/V	0.2224	likely_benign	0.2309	benign	-0.024	Destabilizing	0.951	D	0.441	neutral	None	None	None	None	I
T/W	0.7056	likely_pathogenic	0.6831	pathogenic	-0.769	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
T/Y	0.3237	likely_benign	0.3239	benign	-0.454	Destabilizing	1.0	D	0.709	prob.delet.	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.