TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18215	54868;54869;54870	chr2:178604044;178604043;178604042	chr2:179468771;179468770;179468769
N2AB	16574	49945;49946;49947	chr2:178604044;178604043;178604042	chr2:179468771;179468770;179468769
N2A	15647	47164;47165;47166	chr2:178604044;178604043;178604042	chr2:179468771;179468770;179468769
N2B	9150	27673;27674;27675	chr2:178604044;178604043;178604042	chr2:179468771;179468770;179468769
Novex-1	9275	28048;28049;28050	chr2:178604044;178604043;178604042	chr2:179468771;179468770;179468769
Novex-2	9342	28249;28250;28251	chr2:178604044;178604043;178604042	chr2:179468771;179468770;179468769
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-20
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.3033
• Predicted PPI site: N

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	rs187167219	-0.881	1.0	N	0.703	0.383	None	gnomAD-2.1.1	6.44E-05	None	None	None	None	N	None	6.47E-05	0	None	0	7.24153E-04	None	0	None	0	1.78E-05	0
R/C	rs187167219	-0.881	1.0	N	0.703	0.383	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	3.89864E-04	None	0	0	0	0	0
R/C	rs187167219	-0.881	1.0	N	0.703	0.383	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
R/C	rs187167219	-0.881	1.0	N	0.703	0.383	None	gnomAD-4.0.0	2.04608E-05	None	None	None	None	N	None	1.33472E-05	0	None	0	4.91137E-04	None	0	0	7.63245E-06	0	1.60179E-05
R/H	rs183010574	-1.87	1.0	N	0.661	0.306	0.342865806769	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	1.65728E-04
R/H	rs183010574	-1.87	1.0	N	0.661	0.306	0.342865806769	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs183010574	-1.87	1.0	N	0.661	0.306	0.342865806769	gnomAD-4.0.0	1.24007E-05	None	None	None	None	N	None	1.33608E-05	1.66817E-05	None	0	0	None	0	0	1.01764E-05	2.19713E-05	6.40902E-05
R/P	rs183010574	-0.756	1.0	N	0.773	0.321	None	gnomAD-2.1.1	2.86E-05	None	None	None	None	N	None	4.14E-05	8.48E-05	None	0	0	None	0	None	0	3.13E-05	0
R/P	rs183010574	-0.756	1.0	N	0.773	0.321	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	1.47E-05	0	0
R/P	rs183010574	-0.756	1.0	N	0.773	0.321	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
R/P	rs183010574	-0.756	1.0	N	0.773	0.321	None	gnomAD-4.0.0	8.67985E-06	None	None	None	None	N	None	1.3339E-05	6.67045E-05	None	0	0	None	0	0	7.63236E-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
R/A	0.875	likely_pathogenic	0.8673	pathogenic	-0.772	Destabilizing	0.992	D	0.607	neutral	None	None	None	None	N
R/C	0.6713	likely_pathogenic	0.6442	pathogenic	-0.725	Destabilizing	1.0	D	0.703	prob.neutral	N	0.473623737	None	None	N
R/D	0.9758	likely_pathogenic	0.9777	pathogenic	0.066	Stabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
R/E	0.8826	likely_pathogenic	0.8833	pathogenic	0.204	Stabilizing	0.992	D	0.535	neutral	None	None	None	None	N
R/F	0.9363	likely_pathogenic	0.936	pathogenic	-0.592	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
R/G	0.8673	likely_pathogenic	0.8534	pathogenic	-1.077	Destabilizing	0.998	D	0.659	neutral	N	0.472863268	None	None	N
R/H	0.4162	ambiguous	0.3883	ambiguous	-1.457	Destabilizing	1.0	D	0.661	neutral	N	0.50706973	None	None	N
R/I	0.7875	likely_pathogenic	0.8062	pathogenic	0.047	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
R/K	0.216	likely_benign	0.2494	benign	-0.588	Destabilizing	0.611	D	0.233	neutral	None	None	None	None	N
R/L	0.6865	likely_pathogenic	0.6669	pathogenic	0.047	Stabilizing	0.998	D	0.659	neutral	N	0.490121551	None	None	N
R/M	0.8029	likely_pathogenic	0.8188	pathogenic	-0.397	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
R/N	0.9524	likely_pathogenic	0.9534	pathogenic	-0.215	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
R/P	0.7857	likely_pathogenic	0.7566	pathogenic	-0.205	Destabilizing	1.0	D	0.773	deleterious	N	0.46993828	None	None	N
R/Q	0.3564	ambiguous	0.3451	ambiguous	-0.312	Destabilizing	0.998	D	0.638	neutral	None	None	None	None	N
R/S	0.9479	likely_pathogenic	0.9422	pathogenic	-0.963	Destabilizing	0.996	D	0.681	prob.neutral	N	0.479864485	None	None	N
R/T	0.8346	likely_pathogenic	0.8361	pathogenic	-0.634	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
R/V	0.7968	likely_pathogenic	0.808	pathogenic	-0.205	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
R/W	0.7189	likely_pathogenic	0.6774	pathogenic	-0.299	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
R/Y	0.8832	likely_pathogenic	0.8721	pathogenic	-0.011	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N

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.