TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29689	89290;89291;89292	chr2:178554046;178554045;178554044	chr2:179418773;179418772;179418771
N2AB	28048	84367;84368;84369	chr2:178554046;178554045;178554044	chr2:179418773;179418772;179418771
N2A	27121	81586;81587;81588	chr2:178554046;178554045;178554044	chr2:179418773;179418772;179418771
N2B	20624	62095;62096;62097	chr2:178554046;178554045;178554044	chr2:179418773;179418772;179418771
Novex-1	20749	62470;62471;62472	chr2:178554046;178554045;178554044	chr2:179418773;179418772;179418771
Novex-2	20816	62671;62672;62673	chr2:178554046;178554045;178554044	chr2:179418773;179418772;179418771
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: Fn3-104
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.9292
• 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	rs781635476	-0.111	1.0	N	0.747	0.384	0.591526896791	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
R/C	rs781635476	-0.111	1.0	N	0.747	0.384	0.591526896791	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
R/C	rs781635476	-0.111	1.0	N	0.747	0.384	0.591526896791	gnomAD-4.0.0	1.42536E-05	None	None	None	None	N	None	2.67001E-05	5.00217E-05	None	0	2.22866E-05	None	0	0	1.27138E-05	0	3.20236E-05
R/G	rs781635476	None	1.0	N	0.645	0.345	0.475971816791	gnomAD-4.0.0	6.8422E-07	None	None	None	None	N	None	0	0	None	0	2.51927E-05	None	0	0	0	0	0
R/H	rs368634670	-0.57	1.0	N	0.791	0.304	None	gnomAD-2.1.1	3.57E-05	None	None	None	None	N	None	1.65358E-04	2.83E-05	None	0	0	None	0	None	0	3.91E-05	0
R/H	rs368634670	-0.57	1.0	N	0.791	0.304	None	gnomAD-3.1.2	1.11732E-04	None	None	None	None	N	None	2.89645E-04	0	0	0	0	None	0	0	7.35E-05	0	0
R/H	rs368634670	-0.57	1.0	N	0.791	0.304	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/H	rs368634670	-0.57	1.0	N	0.791	0.304	None	gnomAD-4.0.0	4.39954E-05	None	None	None	None	N	None	1.99936E-04	3.33289E-05	None	0	0	None	0	0	4.49223E-05	1.09796E-05	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	0.5473	ambiguous	0.6582	pathogenic	-0.02	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
R/C	0.2684	likely_benign	0.3266	benign	-0.253	Destabilizing	1.0	D	0.747	deleterious	N	0.489726529	None	None	N
R/D	0.8099	likely_pathogenic	0.8749	pathogenic	-0.161	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/E	0.5783	likely_pathogenic	0.6811	pathogenic	-0.123	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
R/F	0.7105	likely_pathogenic	0.7832	pathogenic	-0.353	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
R/G	0.3523	ambiguous	0.4706	ambiguous	-0.16	Destabilizing	1.0	D	0.645	neutral	N	0.516921364	None	None	N
R/H	0.1606	likely_benign	0.1904	benign	-0.585	Destabilizing	1.0	D	0.791	deleterious	N	0.486579814	None	None	N
R/I	0.4903	ambiguous	0.5656	pathogenic	0.301	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
R/K	0.1477	likely_benign	0.1657	benign	-0.128	Destabilizing	0.998	D	0.553	neutral	None	None	None	None	N
R/L	0.4232	ambiguous	0.5036	ambiguous	0.301	Stabilizing	1.0	D	0.645	neutral	N	0.485657094	None	None	N
R/M	0.48	ambiguous	0.554	ambiguous	-0.056	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
R/N	0.7357	likely_pathogenic	0.81	pathogenic	0.015	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
R/P	0.5492	ambiguous	0.6604	pathogenic	0.212	Stabilizing	1.0	D	0.705	prob.neutral	N	0.444501118	None	None	N
R/Q	0.1589	likely_benign	0.191	benign	-0.069	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
R/S	0.6365	likely_pathogenic	0.7365	pathogenic	-0.262	Destabilizing	1.0	D	0.705	prob.neutral	N	0.435110844	None	None	N
R/T	0.3718	ambiguous	0.4586	ambiguous	-0.115	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
R/V	0.5577	ambiguous	0.637	pathogenic	0.212	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
R/W	0.2184	likely_benign	0.286	benign	-0.49	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
R/Y	0.5096	ambiguous	0.589	pathogenic	-0.079	Destabilizing	1.0	D	0.729	prob.delet.	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.