TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20221	60886;60887;60888	chr2:178591064;178591063;178591062	chr2:179455791;179455790;179455789
N2AB	18580	55963;55964;55965	chr2:178591064;178591063;178591062	chr2:179455791;179455790;179455789
N2A	17653	53182;53183;53184	chr2:178591064;178591063;178591062	chr2:179455791;179455790;179455789
N2B	11156	33691;33692;33693	chr2:178591064;178591063;178591062	chr2:179455791;179455790;179455789
Novex-1	11281	34066;34067;34068	chr2:178591064;178591063;178591062	chr2:179455791;179455790;179455789
Novex-2	11348	34267;34268;34269	chr2:178591064;178591063;178591062	chr2:179455791;179455790;179455789
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: Fn3-34
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.586
• 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
V/A	None	None	0.201	N	0.349	0.114	0.526943034955	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
V/I	rs2050102457	None	0.004	N	0.159	0.045	0.382592752248	gnomAD-4.0.0	1.59214E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85979E-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
V/A	0.1663	likely_benign	0.1719	benign	-0.658	Destabilizing	0.201	N	0.349	neutral	N	0.481808713	None	None	N
V/C	0.6568	likely_pathogenic	0.6326	pathogenic	-0.712	Destabilizing	0.992	D	0.513	neutral	None	None	None	None	N
V/D	0.3787	ambiguous	0.4193	ambiguous	-0.272	Destabilizing	0.896	D	0.559	neutral	N	0.494276578	None	None	N
V/E	0.3148	likely_benign	0.3325	benign	-0.374	Destabilizing	0.92	D	0.557	neutral	None	None	None	None	N
V/F	0.1562	likely_benign	0.1667	benign	-0.761	Destabilizing	0.81	D	0.521	neutral	N	0.521540537	None	None	N
V/G	0.1885	likely_benign	0.2047	benign	-0.82	Destabilizing	0.002	N	0.343	neutral	N	0.475133456	None	None	N
V/H	0.5497	ambiguous	0.567	pathogenic	-0.312	Destabilizing	0.992	D	0.568	neutral	None	None	None	None	N
V/I	0.0667	likely_benign	0.0671	benign	-0.375	Destabilizing	0.004	N	0.159	neutral	N	0.465340537	None	None	N
V/K	0.3513	ambiguous	0.3597	ambiguous	-0.538	Destabilizing	0.85	D	0.547	neutral	None	None	None	None	N
V/L	0.1631	likely_benign	0.1646	benign	-0.375	Destabilizing	0.08	N	0.265	neutral	N	0.466148614	None	None	N
V/M	0.1053	likely_benign	0.1122	benign	-0.38	Destabilizing	0.127	N	0.224	neutral	None	None	None	None	N
V/N	0.2418	likely_benign	0.2613	benign	-0.282	Destabilizing	0.92	D	0.579	neutral	None	None	None	None	N
V/P	0.3544	ambiguous	0.3705	ambiguous	-0.433	Destabilizing	0.972	D	0.577	neutral	None	None	None	None	N
V/Q	0.3276	likely_benign	0.3376	benign	-0.532	Destabilizing	0.92	D	0.581	neutral	None	None	None	None	N
V/R	0.3257	likely_benign	0.3363	benign	0.006	Stabilizing	0.85	D	0.585	neutral	None	None	None	None	N
V/S	0.2056	likely_benign	0.2208	benign	-0.708	Destabilizing	0.617	D	0.507	neutral	None	None	None	None	N
V/T	0.1491	likely_benign	0.1542	benign	-0.706	Destabilizing	0.617	D	0.315	neutral	None	None	None	None	N
V/W	0.7588	likely_pathogenic	0.7653	pathogenic	-0.82	Destabilizing	0.992	D	0.593	neutral	None	None	None	None	N
V/Y	0.5149	ambiguous	0.5184	ambiguous	-0.531	Destabilizing	0.92	D	0.529	neutral	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.