TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8098	24517;24518;24519	chr2:178718908;178718907;178718906	chr2:179583635;179583634;179583633
N2AB	7781	23566;23567;23568	chr2:178718908;178718907;178718906	chr2:179583635;179583634;179583633
N2A	6854	20785;20786;20787	chr2:178718908;178718907;178718906	chr2:179583635;179583634;179583633
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-66
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4451
• 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/S	rs2077908653	None	None	N	0.25	0.167	0.158396225186	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
T/S	rs2077908653	None	None	N	0.25	0.167	0.158396225186	gnomAD-4.0.0	2.56414E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78849E-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
T/A	0.1104	likely_benign	0.093	benign	-1.055	Destabilizing	None	N	0.227	neutral	N	0.49955753	None	None	N
T/C	0.4896	ambiguous	0.3968	ambiguous	-0.785	Destabilizing	0.676	D	0.511	neutral	None	None	None	None	N
T/D	0.529	ambiguous	0.4257	ambiguous	-0.875	Destabilizing	0.072	N	0.449	neutral	None	None	None	None	N
T/E	0.3283	likely_benign	0.2803	benign	-0.824	Destabilizing	0.031	N	0.437	neutral	None	None	None	None	N
T/F	0.2803	likely_benign	0.221	benign	-0.961	Destabilizing	0.214	N	0.553	neutral	None	None	None	None	N
T/G	0.3522	ambiguous	0.2686	benign	-1.362	Destabilizing	0.016	N	0.455	neutral	None	None	None	None	N
T/H	0.2065	likely_benign	0.1821	benign	-1.574	Destabilizing	0.356	N	0.545	neutral	None	None	None	None	N
T/I	0.2124	likely_benign	0.1727	benign	-0.306	Destabilizing	0.029	N	0.497	neutral	N	0.516562603	None	None	N
T/K	0.1494	likely_benign	0.1455	benign	-0.885	Destabilizing	None	N	0.297	neutral	None	None	None	None	N
T/L	0.136	likely_benign	0.11	benign	-0.306	Destabilizing	None	N	0.286	neutral	None	None	None	None	N
T/M	0.1203	likely_benign	0.1088	benign	-0.007	Destabilizing	0.214	N	0.525	neutral	None	None	None	None	N
T/N	0.1832	likely_benign	0.1409	benign	-1.019	Destabilizing	0.055	N	0.389	neutral	N	0.494099801	None	None	N
T/P	0.2455	likely_benign	0.1674	benign	-0.524	Destabilizing	0.055	N	0.545	neutral	N	0.493343013	None	None	N
T/Q	0.1902	likely_benign	0.1767	benign	-1.16	Destabilizing	0.072	N	0.539	neutral	None	None	None	None	N
T/R	0.1092	likely_benign	0.1075	benign	-0.673	Destabilizing	None	N	0.359	neutral	None	None	None	None	N
T/S	0.1211	likely_benign	0.0984	benign	-1.289	Destabilizing	None	N	0.25	neutral	N	0.504910151	None	None	N
T/V	0.1868	likely_benign	0.1565	benign	-0.524	Destabilizing	0.016	N	0.393	neutral	None	None	None	None	N
T/W	0.6042	likely_pathogenic	0.5218	ambiguous	-0.897	Destabilizing	0.864	D	0.579	neutral	None	None	None	None	N
T/Y	0.2943	likely_benign	0.2434	benign	-0.652	Destabilizing	0.356	N	0.548	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.