TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29756	89491;89492;89493	chr2:178553739;178553738;178553737	chr2:179418466;179418465;179418464
N2AB	28115	84568;84569;84570	chr2:178553739;178553738;178553737	chr2:179418466;179418465;179418464
N2A	27188	81787;81788;81789	chr2:178553739;178553738;178553737	chr2:179418466;179418465;179418464
N2B	20691	62296;62297;62298	chr2:178553739;178553738;178553737	chr2:179418466;179418465;179418464
Novex-1	20816	62671;62672;62673	chr2:178553739;178553738;178553737	chr2:179418466;179418465;179418464
Novex-2	20883	62872;62873;62874	chr2:178553739;178553738;178553737	chr2:179418466;179418465;179418464
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-105
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4496
• 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
S/G	None	None	0.425	N	0.245	0.104	0.139678290688	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
S/R	None	None	0.642	N	0.447	0.157	0.260249123532	gnomAD-4.0.0	1.59237E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86007E-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
S/A	0.0992	likely_benign	0.0931	benign	-0.592	Destabilizing	0.176	N	0.195	neutral	None	None	None	None	I
S/C	0.1211	likely_benign	0.1183	benign	-0.44	Destabilizing	0.975	D	0.441	neutral	N	0.507093946	None	None	I
S/D	0.4852	ambiguous	0.5025	ambiguous	-0.611	Destabilizing	0.003	N	0.091	neutral	None	None	None	None	I
S/E	0.5367	ambiguous	0.5472	ambiguous	-0.534	Destabilizing	0.004	N	0.067	neutral	None	None	None	None	I
S/F	0.303	likely_benign	0.2831	benign	-0.551	Destabilizing	0.704	D	0.59	neutral	None	None	None	None	I
S/G	0.0775	likely_benign	0.0787	benign	-0.927	Destabilizing	0.425	N	0.245	neutral	N	0.490951058	None	None	I
S/H	0.4117	ambiguous	0.4236	ambiguous	-1.428	Destabilizing	0.981	D	0.444	neutral	None	None	None	None	I
S/I	0.1814	likely_benign	0.1689	benign	0.212	Stabilizing	0.002	N	0.252	neutral	N	0.486371957	None	None	I
S/K	0.704	likely_pathogenic	0.7174	pathogenic	-0.707	Destabilizing	0.495	N	0.285	neutral	None	None	None	None	I
S/L	0.1162	likely_benign	0.1085	benign	0.212	Stabilizing	0.003	N	0.238	neutral	None	None	None	None	I
S/M	0.171	likely_benign	0.1662	benign	0.286	Stabilizing	0.893	D	0.447	neutral	None	None	None	None	I
S/N	0.1214	likely_benign	0.1313	benign	-0.921	Destabilizing	0.425	N	0.289	neutral	N	0.442234391	None	None	I
S/P	0.7321	likely_pathogenic	0.7636	pathogenic	-0.019	Destabilizing	0.828	D	0.441	neutral	None	None	None	None	I
S/Q	0.4736	ambiguous	0.487	ambiguous	-0.857	Destabilizing	0.704	D	0.288	neutral	None	None	None	None	I
S/R	0.6776	likely_pathogenic	0.6796	pathogenic	-0.808	Destabilizing	0.642	D	0.447	neutral	N	0.460628151	None	None	I
S/T	0.0877	likely_benign	0.0846	benign	-0.755	Destabilizing	0.01	N	0.096	neutral	N	0.440404807	None	None	I
S/V	0.1837	likely_benign	0.1755	benign	-0.019	Destabilizing	0.013	N	0.235	neutral	None	None	None	None	I
S/W	0.4726	ambiguous	0.4572	ambiguous	-0.691	Destabilizing	0.995	D	0.522	neutral	None	None	None	None	I
S/Y	0.2754	likely_benign	0.2664	benign	-0.35	Destabilizing	0.981	D	0.603	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.