TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23790	71593;71594;71595	chr2:178574764;178574763;178574762	chr2:179439491;179439490;179439489
N2AB	22149	66670;66671;66672	chr2:178574764;178574763;178574762	chr2:179439491;179439490;179439489
N2A	21222	63889;63890;63891	chr2:178574764;178574763;178574762	chr2:179439491;179439490;179439489
N2B	14725	44398;44399;44400	chr2:178574764;178574763;178574762	chr2:179439491;179439490;179439489
Novex-1	14850	44773;44774;44775	chr2:178574764;178574763;178574762	chr2:179439491;179439490;179439489
Novex-2	14917	44974;44975;44976	chr2:178574764;178574763;178574762	chr2:179439491;179439490;179439489
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-60
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.9038
• 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
R/C	rs775743818	-0.187	1.0	N	0.639	0.413	0.6544015285	gnomAD-2.1.1	3.23E-05	None	None	None	None	I	None	0	0	None	0	1.03252E-04	None	0	None	4.02E-05	4.72E-05	0
R/C	rs775743818	-0.187	1.0	N	0.639	0.413	0.6544015285	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/C	rs775743818	-0.187	1.0	N	0.639	0.413	0.6544015285	gnomAD-4.0.0	3.41152E-05	None	None	None	None	I	None	1.33576E-05	0	None	0	4.47067E-05	None	0	0	4.3257E-05	0	1.60313E-05
R/G	None	None	0.922	N	0.486	0.333	0.418718287753	gnomAD-4.0.0	6.8487E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00093E-07	0	0
R/H	rs55677134	-0.511	0.159	N	0.363	0.083	None	gnomAD-2.1.1	1.21492E-03	None	None	None	None	I	None	0	1.13733E-04	None	0	1.65119E-02	None	1.97811E-04	None	0	3.15E-05	5.67054E-04
R/H	rs55677134	-0.511	0.159	N	0.363	0.083	None	gnomAD-3.1.2	7.03827E-04	None	None	None	None	I	None	0	6.56E-05	0	0	2.00078E-02	None	0	0	2.94E-05	2.07469E-04	0
R/H	rs55677134	-0.511	0.159	N	0.363	0.083	None	1000 genomes	5.79073E-03	None	None	None	None	I	None	0	0	None	None	2.88E-02	0	None	None	None	0	None
R/H	rs55677134	-0.511	0.159	N	0.363	0.083	None	gnomAD-4.0.0	7.80964E-04	None	None	None	None	I	None	0	8.35031E-05	None	0	2.63581E-02	None	0	0	2.12066E-05	2.09187E-04	4.96779E-04
R/P	None	None	0.988	N	0.563	0.298	0.288352970974	gnomAD-4.0.0	6.84947E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65859E-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
R/A	0.6384	likely_pathogenic	0.5692	pathogenic	0.019	Stabilizing	0.86	D	0.51	neutral	None	None	None	None	I
R/C	0.2371	likely_benign	0.1986	benign	-0.225	Destabilizing	1.0	D	0.639	neutral	N	0.487556801	None	None	I
R/D	0.7937	likely_pathogenic	0.741	pathogenic	-0.278	Destabilizing	0.956	D	0.523	neutral	None	None	None	None	I
R/E	0.6553	likely_pathogenic	0.6033	pathogenic	-0.238	Destabilizing	0.754	D	0.521	neutral	None	None	None	None	I
R/F	0.7502	likely_pathogenic	0.694	pathogenic	-0.289	Destabilizing	0.956	D	0.618	neutral	None	None	None	None	I
R/G	0.3767	ambiguous	0.2778	benign	-0.125	Destabilizing	0.922	D	0.486	neutral	N	0.411822978	None	None	I
R/H	0.1136	likely_benign	0.1056	benign	-0.587	Destabilizing	0.159	N	0.363	neutral	N	0.501583765	None	None	I
R/I	0.6815	likely_pathogenic	0.6507	pathogenic	0.352	Stabilizing	0.978	D	0.615	neutral	None	None	None	None	I
R/K	0.1463	likely_benign	0.1312	benign	-0.144	Destabilizing	0.717	D	0.483	neutral	None	None	None	None	I
R/L	0.4812	ambiguous	0.4384	ambiguous	0.352	Stabilizing	0.976	D	0.476	neutral	N	0.469199056	None	None	I
R/M	0.5874	likely_pathogenic	0.5348	ambiguous	-0.054	Destabilizing	0.998	D	0.523	neutral	None	None	None	None	I
R/N	0.6295	likely_pathogenic	0.5389	ambiguous	-0.024	Destabilizing	0.754	D	0.529	neutral	None	None	None	None	I
R/P	0.8664	likely_pathogenic	0.8298	pathogenic	0.259	Stabilizing	0.988	D	0.563	neutral	N	0.501757123	None	None	I
R/Q	0.1699	likely_benign	0.1456	benign	-0.085	Destabilizing	0.956	D	0.569	neutral	None	None	None	None	I
R/S	0.6635	likely_pathogenic	0.5931	pathogenic	-0.238	Destabilizing	0.922	D	0.521	neutral	N	0.474050447	None	None	I
R/T	0.5774	likely_pathogenic	0.5282	ambiguous	-0.089	Destabilizing	0.978	D	0.509	neutral	None	None	None	None	I
R/V	0.6989	likely_pathogenic	0.673	pathogenic	0.259	Stabilizing	0.978	D	0.603	neutral	None	None	None	None	I
R/W	0.3543	ambiguous	0.3309	benign	-0.449	Destabilizing	0.998	D	0.658	neutral	None	None	None	None	I
R/Y	0.5033	ambiguous	0.4541	ambiguous	-0.044	Destabilizing	0.915	D	0.567	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.