TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9185	27778;27779;27780	chr2:178712369;178712368;178712367	chr2:179577096;179577095;179577094
N2AB	8868	26827;26828;26829	chr2:178712369;178712368;178712367	chr2:179577096;179577095;179577094
N2A	7941	24046;24047;24048	chr2:178712369;178712368;178712367	chr2:179577096;179577095;179577094
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-77
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.3169
• 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/C	rs1477423741	-0.97	0.993	N	0.595	0.448	0.635940165184	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
Y/C	rs1477423741	-0.97	0.993	N	0.595	0.448	0.635940165184	gnomAD-4.0.0	1.59124E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85811E-06	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
Y/A	0.1987	likely_benign	0.2049	benign	-2.378	Highly Destabilizing	0.176	N	0.443	neutral	None	None	None	None	N
Y/C	0.0806	likely_benign	0.0772	benign	-0.827	Destabilizing	0.993	D	0.595	neutral	N	0.508507816	None	None	N
Y/D	0.0836	likely_benign	0.0879	benign	-0.745	Destabilizing	0.27	N	0.494	neutral	N	0.496597312	None	None	N
Y/E	0.2236	likely_benign	0.238	benign	-0.681	Destabilizing	0.013	N	0.427	neutral	None	None	None	None	N
Y/F	0.0744	likely_benign	0.0761	benign	-1.176	Destabilizing	0.784	D	0.466	neutral	N	0.443688334	None	None	N
Y/G	0.2731	likely_benign	0.2699	benign	-2.677	Highly Destabilizing	0.329	N	0.508	neutral	None	None	None	None	N
Y/H	0.0778	likely_benign	0.0825	benign	-0.994	Destabilizing	0.006	N	0.171	neutral	N	0.432471262	None	None	N
Y/I	0.1531	likely_benign	0.1584	benign	-1.48	Destabilizing	0.828	D	0.555	neutral	None	None	None	None	N
Y/K	0.3168	likely_benign	0.327	benign	-0.927	Destabilizing	0.176	N	0.459	neutral	None	None	None	None	N
Y/L	0.2056	likely_benign	0.2056	benign	-1.48	Destabilizing	0.495	N	0.415	neutral	None	None	None	None	N
Y/M	0.3291	likely_benign	0.3278	benign	-1.019	Destabilizing	0.981	D	0.523	neutral	None	None	None	None	N
Y/N	0.0676	likely_benign	0.0719	benign	-1.099	Destabilizing	0.425	N	0.499	neutral	N	0.457097561	None	None	N
Y/P	0.939	likely_pathogenic	0.9242	pathogenic	-1.773	Destabilizing	0.828	D	0.604	neutral	None	None	None	None	N
Y/Q	0.1841	likely_benign	0.1973	benign	-1.133	Destabilizing	0.037	N	0.241	neutral	None	None	None	None	N
Y/R	0.1928	likely_benign	0.2004	benign	-0.369	Destabilizing	0.003	N	0.417	neutral	None	None	None	None	N
Y/S	0.0735	likely_benign	0.0771	benign	-1.715	Destabilizing	0.01	N	0.417	neutral	N	0.41059448	None	None	N
Y/T	0.1474	likely_benign	0.1547	benign	-1.56	Destabilizing	0.329	N	0.503	neutral	None	None	None	None	N
Y/V	0.1316	likely_benign	0.1353	benign	-1.773	Destabilizing	0.495	N	0.445	neutral	None	None	None	None	N
Y/W	0.3692	ambiguous	0.363	ambiguous	-0.731	Destabilizing	0.981	D	0.519	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.