TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26890	80893;80894;80895	chr2:178565464;178565463;178565462	chr2:179430191;179430190;179430189
N2AB	25249	75970;75971;75972	chr2:178565464;178565463;178565462	chr2:179430191;179430190;179430189
N2A	24322	73189;73190;73191	chr2:178565464;178565463;178565462	chr2:179430191;179430190;179430189
N2B	17825	53698;53699;53700	chr2:178565464;178565463;178565462	chr2:179430191;179430190;179430189
Novex-1	17950	54073;54074;54075	chr2:178565464;178565463;178565462	chr2:179430191;179430190;179430189
Novex-2	18017	54274;54275;54276	chr2:178565464;178565463;178565462	chr2:179430191;179430190;179430189
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: Ig-139
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.7039
• 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/N	rs766880487	0.155	None	N	0.164	0.125	0.162503812791	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
S/N	rs766880487	0.155	None	N	0.164	0.125	0.162503812791	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
S/N	rs766880487	0.155	None	N	0.164	0.125	0.162503812791	gnomAD-4.0.0	7.43908E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.01732E-05	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	0.1355	likely_benign	0.136	benign	-0.298	Destabilizing	0.035	N	0.358	neutral	None	None	None	None	I
S/C	0.1321	likely_benign	0.153	benign	-0.293	Destabilizing	0.78	D	0.371	neutral	N	0.519245175	None	None	I
S/D	0.8101	likely_pathogenic	0.8399	pathogenic	0.643	Stabilizing	0.081	N	0.264	neutral	None	None	None	None	I
S/E	0.8794	likely_pathogenic	0.899	pathogenic	0.649	Stabilizing	0.149	N	0.263	neutral	None	None	None	None	I
S/F	0.4334	ambiguous	0.4277	ambiguous	-0.638	Destabilizing	0.555	D	0.44	neutral	None	None	None	None	I
S/G	0.149	likely_benign	0.1728	benign	-0.513	Destabilizing	0.027	N	0.277	neutral	N	0.503089476	None	None	I
S/H	0.4926	ambiguous	0.5424	ambiguous	-0.78	Destabilizing	0.555	D	0.357	neutral	None	None	None	None	I
S/I	0.2758	likely_benign	0.2945	benign	0.158	Stabilizing	0.188	N	0.431	neutral	N	0.506507661	None	None	I
S/K	0.9248	likely_pathogenic	0.9449	pathogenic	-0.076	Destabilizing	0.149	N	0.261	neutral	None	None	None	None	I
S/L	0.1871	likely_benign	0.1812	benign	0.158	Stabilizing	0.081	N	0.379	neutral	None	None	None	None	I
S/M	0.2755	likely_benign	0.2531	benign	-0.031	Destabilizing	0.824	D	0.358	neutral	None	None	None	None	I
S/N	0.1654	likely_benign	0.1783	benign	-0.14	Destabilizing	None	N	0.164	neutral	N	0.498618897	None	None	I
S/P	0.6676	likely_pathogenic	0.6585	pathogenic	0.039	Stabilizing	0.555	D	0.36	neutral	None	None	None	None	I
S/Q	0.7288	likely_pathogenic	0.7666	pathogenic	-0.154	Destabilizing	0.555	D	0.307	neutral	None	None	None	None	I
S/R	0.8873	likely_pathogenic	0.9111	pathogenic	-0.058	Destabilizing	0.317	N	0.349	neutral	N	0.510566687	None	None	I
S/T	0.0934	likely_benign	0.0853	benign	-0.185	Destabilizing	None	N	0.164	neutral	N	0.448208719	None	None	I
S/V	0.2676	likely_benign	0.2732	benign	0.039	Stabilizing	0.081	N	0.429	neutral	None	None	None	None	I
S/W	0.6347	likely_pathogenic	0.6489	pathogenic	-0.715	Destabilizing	0.935	D	0.561	neutral	None	None	None	None	I
S/Y	0.3337	likely_benign	0.3593	ambiguous	-0.35	Destabilizing	0.555	D	0.439	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.