TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9947	30064;30065;30066	chr2:178704633;178704632;178704631	chr2:179569360;179569359;179569358
N2AB	9630	29113;29114;29115	chr2:178704633;178704632;178704631	chr2:179569360;179569359;179569358
N2A	8703	26332;26333;26334	chr2:178704633;178704632;178704631	chr2:179569360;179569359;179569358
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-84
• Domain position: 48
• Structural Position: 121
• Q(SASA): 0.124
• 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/C	None	None	0.915	None	0.551	0.416	0.608671624233	gnomAD-4.0.0	6.8478E-07	None	None	None	None	N	None	0	0	None	0	2.51965E-05	None	0	0	0	0	0
F/S	None	None	0.117	None	0.533	0.392	0.509109621728	gnomAD-4.0.0	6.8478E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00017E-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
F/A	0.9361	likely_pathogenic	0.9642	pathogenic	-2.784	Highly Destabilizing	0.149	N	0.529	neutral	None	None	None	None	N
F/C	0.6937	likely_pathogenic	0.7909	pathogenic	-1.943	Destabilizing	0.915	D	0.551	neutral	None	None	None	None	N
F/D	0.9802	likely_pathogenic	0.9853	pathogenic	-2.735	Highly Destabilizing	0.555	D	0.607	neutral	None	None	None	None	N
F/E	0.9828	likely_pathogenic	0.9881	pathogenic	-2.563	Highly Destabilizing	0.262	N	0.6	neutral	None	None	None	None	N
F/G	0.9753	likely_pathogenic	0.9856	pathogenic	-3.218	Highly Destabilizing	0.262	N	0.587	neutral	None	None	None	None	N
F/H	0.7825	likely_pathogenic	0.8176	pathogenic	-1.651	Destabilizing	0.38	N	0.545	neutral	None	None	None	None	N
F/I	0.6338	likely_pathogenic	0.7109	pathogenic	-1.399	Destabilizing	0.117	N	0.511	neutral	None	None	None	None	N
F/K	0.9789	likely_pathogenic	0.9858	pathogenic	-2.139	Highly Destabilizing	0.38	N	0.6	neutral	None	None	None	None	N
F/L	0.9619	likely_pathogenic	0.9725	pathogenic	-1.399	Destabilizing	0.027	N	0.415	neutral	None	None	None	None	N
F/M	0.857	likely_pathogenic	0.8809	pathogenic	-1.11	Destabilizing	0.555	D	0.539	neutral	None	None	None	None	N
F/N	0.9021	likely_pathogenic	0.9244	pathogenic	-2.479	Highly Destabilizing	0.555	D	0.621	neutral	None	None	None	None	N
F/P	0.999	likely_pathogenic	0.9994	pathogenic	-1.867	Destabilizing	0.791	D	0.623	neutral	None	None	None	None	N
F/Q	0.9689	likely_pathogenic	0.9788	pathogenic	-2.471	Highly Destabilizing	0.555	D	0.628	neutral	None	None	None	None	N
F/R	0.9524	likely_pathogenic	0.9699	pathogenic	-1.537	Destabilizing	0.38	N	0.623	neutral	None	None	None	None	N
F/S	0.8785	likely_pathogenic	0.9269	pathogenic	-3.203	Highly Destabilizing	0.117	N	0.533	neutral	None	None	None	None	N
F/T	0.8643	likely_pathogenic	0.9049	pathogenic	-2.918	Highly Destabilizing	0.149	N	0.535	neutral	None	None	None	None	N
F/V	0.6057	likely_pathogenic	0.6942	pathogenic	-1.867	Destabilizing	0.117	N	0.537	neutral	None	None	None	None	N
F/W	0.5577	ambiguous	0.5723	pathogenic	-0.539	Destabilizing	0.555	D	0.55	neutral	None	None	None	None	N
F/Y	0.1032	likely_benign	0.1175	benign	-0.87	Destabilizing	None	N	0.131	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.