TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31660	95203;95204;95205	chr2:178546353;178546352;178546351	chr2:179411080;179411079;179411078
N2AB	30019	90280;90281;90282	chr2:178546353;178546352;178546351	chr2:179411080;179411079;179411078
N2A	29092	87499;87500;87501	chr2:178546353;178546352;178546351	chr2:179411080;179411079;179411078
N2B	22595	68008;68009;68010	chr2:178546353;178546352;178546351	chr2:179411080;179411079;179411078
Novex-1	22720	68383;68384;68385	chr2:178546353;178546352;178546351	chr2:179411080;179411079;179411078
Novex-2	22787	68584;68585;68586	chr2:178546353;178546352;178546351	chr2:179411080;179411079;179411078
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-152
• Domain position: 40
• Structural Position: 102
• Q(SASA): 0.7955
• 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
E/G	None	None	1.0	N	0.563	0.454	0.392395365052	gnomAD-4.0.0	1.59124E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85834E-06	0	0
E/K	None	None	0.999	N	0.589	0.381	0.316198179892	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-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
E/A	0.3346	likely_benign	0.3358	benign	-0.007	Destabilizing	0.999	D	0.563	neutral	N	0.455112396	None	None	N
E/C	0.9385	likely_pathogenic	0.943	pathogenic	-0.296	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/D	0.1366	likely_benign	0.1466	benign	-0.343	Destabilizing	0.999	D	0.457	neutral	N	0.424634773	None	None	N
E/F	0.9402	likely_pathogenic	0.9458	pathogenic	-0.081	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/G	0.2199	likely_benign	0.2326	benign	-0.1	Destabilizing	1.0	D	0.563	neutral	N	0.459131349	None	None	N
E/H	0.6489	likely_pathogenic	0.6758	pathogenic	0.578	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/I	0.7619	likely_pathogenic	0.7739	pathogenic	0.176	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/K	0.2778	likely_benign	0.2908	benign	0.31	Stabilizing	0.999	D	0.589	neutral	N	0.462481085	None	None	N
E/L	0.7021	likely_pathogenic	0.7177	pathogenic	0.176	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/M	0.7719	likely_pathogenic	0.7855	pathogenic	-0.088	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
E/N	0.4004	ambiguous	0.4154	ambiguous	0.114	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/P	0.4674	ambiguous	0.4873	ambiguous	0.132	Stabilizing	1.0	D	0.588	neutral	None	None	None	None	N
E/Q	0.2165	likely_benign	0.2308	benign	0.116	Stabilizing	1.0	D	0.565	neutral	N	0.497383093	None	None	N
E/R	0.409	ambiguous	0.433	ambiguous	0.546	Stabilizing	1.0	D	0.658	neutral	None	None	None	None	N
E/S	0.2969	likely_benign	0.306	benign	-0.034	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
E/T	0.4765	ambiguous	0.4814	ambiguous	0.052	Stabilizing	1.0	D	0.581	neutral	None	None	None	None	N
E/V	0.5514	ambiguous	0.5674	pathogenic	0.132	Stabilizing	1.0	D	0.599	neutral	N	0.474254123	None	None	N
E/W	0.9575	likely_pathogenic	0.9646	pathogenic	-0.057	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/Y	0.8427	likely_pathogenic	0.8551	pathogenic	0.131	Stabilizing	1.0	D	0.627	neutral	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.