TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5788	17587;17588;17589	chr2:178731404;178731403;178731402	chr2:179596131;179596130;179596129
N2AB	5471	16636;16637;16638	chr2:178731404;178731403;178731402	chr2:179596131;179596130;179596129
N2A	4544	13855;13856;13857	chr2:178731404;178731403;178731402	chr2:179596131;179596130;179596129
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-41
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.3595
• 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
Y/H	rs1484048025	-1.051	0.006	N	0.285	0.253	0.227260227426	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Y/H	rs1484048025	-1.051	0.006	N	0.285	0.253	0.227260227426	gnomAD-4.0.0	1.59121E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-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
Y/A	0.4146	ambiguous	0.3823	ambiguous	-2.165	Highly Destabilizing	0.013	N	0.404	neutral	None	None	None	None	N
Y/C	0.1337	likely_benign	0.1362	benign	-0.755	Destabilizing	0.975	D	0.516	neutral	N	0.497733462	None	None	N
Y/D	0.3103	likely_benign	0.2983	benign	-0.499	Destabilizing	0.642	D	0.517	neutral	N	0.483476086	None	None	N
Y/E	0.4779	ambiguous	0.444	ambiguous	-0.436	Destabilizing	0.704	D	0.548	neutral	None	None	None	None	N
Y/F	0.083	likely_benign	0.0757	benign	-0.984	Destabilizing	0.006	N	0.293	neutral	N	0.482956011	None	None	N
Y/G	0.4738	ambiguous	0.4706	ambiguous	-2.467	Highly Destabilizing	0.495	N	0.483	neutral	None	None	None	None	N
Y/H	0.1218	likely_benign	0.1083	benign	-0.883	Destabilizing	0.006	N	0.285	neutral	N	0.435164851	None	None	N
Y/I	0.2714	likely_benign	0.2313	benign	-1.267	Destabilizing	0.543	D	0.488	neutral	None	None	None	None	N
Y/K	0.4359	ambiguous	0.4034	ambiguous	-0.899	Destabilizing	0.704	D	0.551	neutral	None	None	None	None	N
Y/L	0.2595	likely_benign	0.2347	benign	-1.267	Destabilizing	0.003	N	0.307	neutral	None	None	None	None	N
Y/M	0.4553	ambiguous	0.4254	ambiguous	-0.865	Destabilizing	0.176	N	0.382	neutral	None	None	None	None	N
Y/N	0.1625	likely_benign	0.1552	benign	-1.1	Destabilizing	0.642	D	0.525	neutral	N	0.489401981	None	None	N
Y/P	0.9514	likely_pathogenic	0.9533	pathogenic	-1.559	Destabilizing	0.944	D	0.567	neutral	None	None	None	None	N
Y/Q	0.2816	likely_benign	0.2542	benign	-1.086	Destabilizing	0.704	D	0.547	neutral	None	None	None	None	N
Y/R	0.2643	likely_benign	0.2413	benign	-0.413	Destabilizing	0.704	D	0.55	neutral	None	None	None	None	N
Y/S	0.1571	likely_benign	0.1503	benign	-1.687	Destabilizing	0.065	N	0.424	neutral	N	0.46689048	None	None	N
Y/T	0.3047	likely_benign	0.2763	benign	-1.532	Destabilizing	0.543	D	0.537	neutral	None	None	None	None	N
Y/V	0.2397	likely_benign	0.2131	benign	-1.559	Destabilizing	0.329	N	0.441	neutral	None	None	None	None	N
Y/W	0.4026	ambiguous	0.3736	ambiguous	-0.609	Destabilizing	0.981	D	0.529	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.