TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6046	18361;18362;18363	chr2:178730264;178730263;178730262	chr2:179594991;179594990;179594989
N2AB	5729	17410;17411;17412	chr2:178730264;178730263;178730262	chr2:179594991;179594990;179594989
N2A	4802	14629;14630;14631	chr2:178730264;178730263;178730262	chr2:179594991;179594990;179594989
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-44
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1462
• 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
F/L	None	None	0.994	N	0.517	0.418	0.316198179892	gnomAD-4.0.0	1.59284E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41429E-04	0	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
F/A	0.935	likely_pathogenic	0.9052	pathogenic	-2.798	Highly Destabilizing	0.983	D	0.573	neutral	None	None	None	None	N
F/C	0.7687	likely_pathogenic	0.6594	pathogenic	-1.402	Destabilizing	1.0	D	0.701	prob.neutral	N	0.500805075	None	None	N
F/D	0.9711	likely_pathogenic	0.9652	pathogenic	-2.797	Highly Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
F/E	0.946	likely_pathogenic	0.9342	pathogenic	-2.658	Highly Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
F/G	0.9532	likely_pathogenic	0.9376	pathogenic	-3.167	Highly Destabilizing	0.992	D	0.681	prob.neutral	None	None	None	None	N
F/H	0.7212	likely_pathogenic	0.6649	pathogenic	-1.515	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
F/I	0.583	likely_pathogenic	0.5115	ambiguous	-1.617	Destabilizing	0.998	D	0.603	neutral	N	0.459530456	None	None	N
F/K	0.9293	likely_pathogenic	0.8979	pathogenic	-1.772	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
F/L	0.9335	likely_pathogenic	0.8948	pathogenic	-1.617	Destabilizing	0.994	D	0.517	neutral	N	0.456304474	None	None	N
F/M	0.7487	likely_pathogenic	0.667	pathogenic	-1.175	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
F/N	0.8587	likely_pathogenic	0.8248	pathogenic	-2.021	Highly Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	N
F/P	0.9997	likely_pathogenic	0.9996	pathogenic	-2.016	Highly Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
F/Q	0.8732	likely_pathogenic	0.8353	pathogenic	-2.116	Highly Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
F/R	0.8589	likely_pathogenic	0.8191	pathogenic	-1.064	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
F/S	0.8148	likely_pathogenic	0.7565	pathogenic	-2.651	Highly Destabilizing	0.889	D	0.502	neutral	N	0.499500678	None	None	N
F/T	0.8538	likely_pathogenic	0.8044	pathogenic	-2.425	Highly Destabilizing	0.983	D	0.643	neutral	None	None	None	None	N
F/V	0.6191	likely_pathogenic	0.5427	ambiguous	-2.016	Highly Destabilizing	0.994	D	0.596	neutral	N	0.458049199	None	None	N
F/W	0.5358	ambiguous	0.4984	ambiguous	-0.56	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
F/Y	0.1599	likely_benign	0.1361	benign	-0.864	Destabilizing	0.998	D	0.532	neutral	N	0.44841571	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.