TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5322	16189;16190;16191	chr2:178733329;178733328;178733327	chr2:179598056;179598055;179598054
N2AB	5005	15238;15239;15240	chr2:178733329;178733328;178733327	chr2:179598056;179598055;179598054
N2A	4078	12457;12458;12459	chr2:178733329;178733328;178733327	chr2:179598056;179598055;179598054
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-36
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.6191
• 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/L	rs758182029	0.016	0.896	D	0.502	0.339	0.437527004654	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	8.9E-06	0
S/L	rs758182029	0.016	0.896	D	0.502	0.339	0.437527004654	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
S/L	rs758182029	0.016	0.896	D	0.502	0.339	0.437527004654	gnomAD-4.0.0	2.35488E-05	None	None	None	None	I	None	0	1.667E-05	None	0	0	None	0	0	3.05142E-05	0	1.60133E-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
S/A	0.0707	likely_benign	0.0771	benign	-0.511	Destabilizing	0.026	N	0.267	neutral	N	0.455195604	None	None	I
S/C	0.1837	likely_benign	0.1658	benign	-0.364	Destabilizing	0.997	D	0.453	neutral	None	None	None	None	I
S/D	0.5772	likely_pathogenic	0.5609	ambiguous	-0.295	Destabilizing	0.959	D	0.395	neutral	None	None	None	None	I
S/E	0.6666	likely_pathogenic	0.6456	pathogenic	-0.327	Destabilizing	0.919	D	0.416	neutral	None	None	None	None	I
S/F	0.2793	likely_benign	0.24	benign	-0.753	Destabilizing	0.988	D	0.577	neutral	None	None	None	None	I
S/G	0.1199	likely_benign	0.1273	benign	-0.735	Destabilizing	0.851	D	0.423	neutral	None	None	None	None	I
S/H	0.4518	ambiguous	0.4302	ambiguous	-1.292	Destabilizing	0.999	D	0.447	neutral	None	None	None	None	I
S/I	0.2914	likely_benign	0.2702	benign	-0.035	Destabilizing	0.976	D	0.553	neutral	None	None	None	None	I
S/K	0.7792	likely_pathogenic	0.7504	pathogenic	-0.745	Destabilizing	0.919	D	0.411	neutral	None	None	None	None	I
S/L	0.1079	likely_benign	0.108	benign	-0.035	Destabilizing	0.896	D	0.502	neutral	D	0.592309442	None	None	I
S/M	0.2295	likely_benign	0.2324	benign	0.269	Stabilizing	0.999	D	0.438	neutral	None	None	None	None	I
S/N	0.215	likely_benign	0.2234	benign	-0.601	Destabilizing	0.959	D	0.451	neutral	None	None	None	None	I
S/P	0.6509	likely_pathogenic	0.681	pathogenic	-0.16	Destabilizing	0.984	D	0.427	neutral	N	0.516449955	None	None	I
S/Q	0.5905	likely_pathogenic	0.5821	pathogenic	-0.8	Destabilizing	0.988	D	0.384	neutral	None	None	None	None	I
S/R	0.7034	likely_pathogenic	0.6653	pathogenic	-0.592	Destabilizing	0.988	D	0.424	neutral	None	None	None	None	I
S/T	0.0878	likely_benign	0.0972	benign	-0.612	Destabilizing	0.046	N	0.234	neutral	N	0.513721747	None	None	I
S/V	0.2281	likely_benign	0.2266	benign	-0.16	Destabilizing	0.851	D	0.516	neutral	None	None	None	None	I
S/W	0.4822	ambiguous	0.444	ambiguous	-0.753	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
S/Y	0.2558	likely_benign	0.2157	benign	-0.494	Destabilizing	0.996	D	0.577	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.