TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31242	93949;93950;93951	chr2:178547902;178547901;178547900	chr2:179412629;179412628;179412627
N2AB	29601	89026;89027;89028	chr2:178547902;178547901;178547900	chr2:179412629;179412628;179412627
N2A	28674	86245;86246;86247	chr2:178547902;178547901;178547900	chr2:179412629;179412628;179412627
N2B	22177	66754;66755;66756	chr2:178547902;178547901;178547900	chr2:179412629;179412628;179412627
Novex-1	22302	67129;67130;67131	chr2:178547902;178547901;178547900	chr2:179412629;179412628;179412627
Novex-2	22369	67330;67331;67332	chr2:178547902;178547901;178547900	chr2:179412629;179412628;179412627
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: Ig-151
• Domain position: 25
• Structural Position: 41
• Q(SASA): 0.6955
• 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	rs563887822	-0.094	1.0	N	0.761	0.47	0.637288232684	gnomAD-2.1.1	3.21E-05	None	None	None	None	I	None	4.13E-05	0	None	0	0	None	3.27E-05	None	0	5.47E-05	0
R/C	rs563887822	-0.094	1.0	N	0.761	0.47	0.637288232684	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	2.41E-05	0	0	0	1.92678E-04	None	0	0	5.88E-05	2.07125E-04	0
R/C	rs563887822	-0.094	1.0	N	0.761	0.47	0.637288232684	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/C	rs563887822	-0.094	1.0	N	0.761	0.47	0.637288232684	gnomAD-4.0.0	4.2756E-05	None	None	None	None	I	None	1.33273E-05	0	None	0	2.22955E-05	None	0	0	5.00071E-05	4.39252E-05	6.40205E-05
R/H	rs369899675	-0.805	1.0	D	0.765	0.434	None	gnomAD-2.1.1	9.64E-05	None	None	None	None	I	None	4.13E-05	2.83E-05	None	0	1.18009E-03	None	0	None	0	1.56E-05	0
R/H	rs369899675	-0.805	1.0	D	0.765	0.434	None	gnomAD-3.1.2	6.58E-05	None	None	None	None	I	None	4.83E-05	6.56E-05	0	0	5.78481E-04	None	0	0	2.94E-05	0	9.56938E-04
R/H	rs369899675	-0.805	1.0	D	0.765	0.434	None	gnomAD-4.0.0	4.4E-05	None	None	None	None	I	None	5.34245E-05	3.33567E-05	None	0	5.79555E-04	None	0	3.28947E-04	2.8818E-05	0	4.80323E-05
R/L	rs369899675	None	1.0	N	0.639	0.463	0.598660209896	gnomAD-4.0.0	6.84195E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99437E-07	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	0.8692	likely_pathogenic	0.8361	pathogenic	-0.014	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
R/C	0.3033	likely_benign	0.2539	benign	-0.301	Destabilizing	1.0	D	0.761	deleterious	N	0.505304749	None	None	I
R/D	0.9687	likely_pathogenic	0.9646	pathogenic	-0.346	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
R/E	0.8062	likely_pathogenic	0.7734	pathogenic	-0.317	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
R/F	0.7775	likely_pathogenic	0.7349	pathogenic	-0.364	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
R/G	0.8303	likely_pathogenic	0.8017	pathogenic	-0.13	Destabilizing	1.0	D	0.639	neutral	N	0.505051259	None	None	I
R/H	0.1898	likely_benign	0.1791	benign	-0.608	Destabilizing	1.0	D	0.765	deleterious	D	0.525016064	None	None	I
R/I	0.4677	ambiguous	0.3888	ambiguous	0.245	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
R/K	0.1934	likely_benign	0.1941	benign	-0.238	Destabilizing	0.998	D	0.522	neutral	None	None	None	None	I
R/L	0.5154	ambiguous	0.4439	ambiguous	0.245	Stabilizing	1.0	D	0.639	neutral	N	0.508238457	None	None	I
R/M	0.613	likely_pathogenic	0.5235	ambiguous	-0.142	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
R/N	0.9048	likely_pathogenic	0.8911	pathogenic	-0.152	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
R/P	0.9863	likely_pathogenic	0.9842	pathogenic	0.175	Stabilizing	1.0	D	0.712	prob.delet.	N	0.493948443	None	None	I
R/Q	0.1931	likely_benign	0.1742	benign	-0.184	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
R/S	0.8757	likely_pathogenic	0.8604	pathogenic	-0.308	Destabilizing	1.0	D	0.675	prob.neutral	N	0.478203552	None	None	I
R/T	0.7344	likely_pathogenic	0.6697	pathogenic	-0.185	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
R/V	0.6411	likely_pathogenic	0.5844	pathogenic	0.175	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
R/W	0.3146	likely_benign	0.2576	benign	-0.569	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
R/Y	0.5712	likely_pathogenic	0.5214	ambiguous	-0.175	Destabilizing	1.0	D	0.74	deleterious	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.