TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27792	83599;83600;83601	chr2:178562758;178562757;178562756	chr2:179427485;179427484;179427483
N2AB	26151	78676;78677;78678	chr2:178562758;178562757;178562756	chr2:179427485;179427484;179427483
N2A	25224	75895;75896;75897	chr2:178562758;178562757;178562756	chr2:179427485;179427484;179427483
N2B	18727	56404;56405;56406	chr2:178562758;178562757;178562756	chr2:179427485;179427484;179427483
Novex-1	18852	56779;56780;56781	chr2:178562758;178562757;178562756	chr2:179427485;179427484;179427483
Novex-2	18919	56980;56981;56982	chr2:178562758;178562757;178562756	chr2:179427485;179427484;179427483
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-90
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.6013
• 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
I/T	rs747559346	-0.361	0.822	N	0.456	0.305	0.517709844387	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	6.55E-05	None	0	8.9E-06	0
I/T	rs747559346	-0.361	0.822	N	0.456	0.305	0.517709844387	gnomAD-4.0.0	7.5308E-06	None	None	None	None	I	None	0	2.24024E-05	None	0	0	None	0	0	6.29845E-06	2.32094E-05	1.65848E-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
I/A	0.4162	ambiguous	0.4533	ambiguous	-0.663	Destabilizing	0.86	D	0.471	neutral	None	None	None	None	I
I/C	0.8272	likely_pathogenic	0.8417	pathogenic	-0.668	Destabilizing	0.998	D	0.521	neutral	None	None	None	None	I
I/D	0.8436	likely_pathogenic	0.8735	pathogenic	0.134	Stabilizing	0.019	N	0.388	neutral	None	None	None	None	I
I/E	0.7765	likely_pathogenic	0.8144	pathogenic	0.052	Stabilizing	0.754	D	0.532	neutral	None	None	None	None	I
I/F	0.2798	likely_benign	0.3068	benign	-0.642	Destabilizing	0.99	D	0.422	neutral	N	0.459659785	None	None	I
I/G	0.8112	likely_pathogenic	0.8411	pathogenic	-0.832	Destabilizing	0.956	D	0.537	neutral	None	None	None	None	I
I/H	0.6937	likely_pathogenic	0.7371	pathogenic	-0.161	Destabilizing	0.998	D	0.63	neutral	None	None	None	None	I
I/K	0.7236	likely_pathogenic	0.7747	pathogenic	-0.263	Destabilizing	0.956	D	0.651	neutral	None	None	None	None	I
I/L	0.0907	likely_benign	0.1005	benign	-0.341	Destabilizing	0.795	D	0.317	neutral	N	0.451963021	None	None	I
I/M	0.1221	likely_benign	0.1303	benign	-0.371	Destabilizing	0.99	D	0.428	neutral	N	0.508395094	None	None	I
I/N	0.3638	ambiguous	0.4001	ambiguous	-0.084	Destabilizing	0.89	D	0.653	neutral	N	0.383372515	None	None	I
I/P	0.9259	likely_pathogenic	0.9281	pathogenic	-0.415	Destabilizing	0.978	D	0.663	neutral	None	None	None	None	I
I/Q	0.6465	likely_pathogenic	0.6914	pathogenic	-0.282	Destabilizing	0.978	D	0.664	neutral	None	None	None	None	I
I/R	0.611	likely_pathogenic	0.6599	pathogenic	0.222	Stabilizing	0.978	D	0.664	neutral	None	None	None	None	I
I/S	0.3946	ambiguous	0.4311	ambiguous	-0.603	Destabilizing	0.822	D	0.483	neutral	N	0.447210562	None	None	I
I/T	0.201	likely_benign	0.1918	benign	-0.572	Destabilizing	0.822	D	0.456	neutral	N	0.465238963	None	None	I
I/V	0.1251	likely_benign	0.1193	benign	-0.415	Destabilizing	0.795	D	0.351	neutral	N	0.473223728	None	None	I
I/W	0.832	likely_pathogenic	0.8513	pathogenic	-0.647	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	I
I/Y	0.6683	likely_pathogenic	0.6974	pathogenic	-0.389	Destabilizing	0.993	D	0.501	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.