TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9083	27472;27473;27474	chr2:178712778;178712777;178712776	chr2:179577505;179577504;179577503
N2AB	8766	26521;26522;26523	chr2:178712778;178712777;178712776	chr2:179577505;179577504;179577503
N2A	7839	23740;23741;23742	chr2:178712778;178712777;178712776	chr2:179577505;179577504;179577503
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: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-76
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.5948
• 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
T/A	None	None	0.001	N	0.086	0.022	0.0401082797425	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
T/I	None	None	0.002	N	0.212	0.04	0.117506650769	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02407E-05

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	0.0607	likely_benign	0.0602	benign	-0.545	Destabilizing	0.001	N	0.086	neutral	N	0.41657265	None	None	N
T/C	0.3069	likely_benign	0.3097	benign	-0.23	Destabilizing	0.836	D	0.254	neutral	None	None	None	None	N
T/D	0.1848	likely_benign	0.1808	benign	0.173	Stabilizing	0.418	N	0.265	neutral	None	None	None	None	N
T/E	0.1624	likely_benign	0.1628	benign	0.092	Stabilizing	0.418	N	0.255	neutral	None	None	None	None	N
T/F	0.1282	likely_benign	0.1347	benign	-1.074	Destabilizing	0.716	D	0.339	neutral	None	None	None	None	N
T/G	0.1621	likely_benign	0.1456	benign	-0.667	Destabilizing	0.129	N	0.236	neutral	None	None	None	None	N
T/H	0.1505	likely_benign	0.1465	benign	-1.028	Destabilizing	0.94	D	0.277	neutral	None	None	None	None	N
T/I	0.0742	likely_benign	0.0802	benign	-0.342	Destabilizing	0.002	N	0.212	neutral	N	0.429387232	None	None	N
T/K	0.1285	likely_benign	0.1308	benign	-0.346	Destabilizing	0.101	N	0.26	neutral	N	0.39556266	None	None	N
T/L	0.0629	likely_benign	0.0632	benign	-0.342	Destabilizing	0.049	N	0.285	neutral	None	None	None	None	N
T/M	0.0746	likely_benign	0.0759	benign	0.024	Stabilizing	0.061	N	0.27	neutral	None	None	None	None	N
T/N	0.0827	likely_benign	0.0805	benign	-0.096	Destabilizing	0.418	N	0.216	neutral	None	None	None	None	N
T/P	0.0699	likely_benign	0.069	benign	-0.383	Destabilizing	0.001	N	0.178	neutral	N	0.366663905	None	None	N
T/Q	0.1499	likely_benign	0.1448	benign	-0.379	Destabilizing	0.716	D	0.34	neutral	None	None	None	None	N
T/R	0.1026	likely_benign	0.1078	benign	-0.074	Destabilizing	0.002	N	0.193	neutral	N	0.397120098	None	None	N
T/S	0.0798	likely_benign	0.0744	benign	-0.345	Destabilizing	0.021	N	0.148	neutral	N	0.437737356	None	None	N
T/V	0.0793	likely_benign	0.0812	benign	-0.383	Destabilizing	0.049	N	0.184	neutral	None	None	None	None	N
T/W	0.422	ambiguous	0.4352	ambiguous	-1.03	Destabilizing	0.983	D	0.296	neutral	None	None	None	None	N
T/Y	0.1516	likely_benign	0.1608	benign	-0.76	Destabilizing	0.836	D	0.294	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.