TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28311	85156;85157;85158	chr2:178561201;178561200;178561199	chr2:179425928;179425927;179425926
N2AB	26670	80233;80234;80235	chr2:178561201;178561200;178561199	chr2:179425928;179425927;179425926
N2A	25743	77452;77453;77454	chr2:178561201;178561200;178561199	chr2:179425928;179425927;179425926
N2B	19246	57961;57962;57963	chr2:178561201;178561200;178561199	chr2:179425928;179425927;179425926
Novex-1	19371	58336;58337;58338	chr2:178561201;178561200;178561199	chr2:179425928;179425927;179425926
Novex-2	19438	58537;58538;58539	chr2:178561201;178561200;178561199	chr2:179425928;179425927;179425926
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: Fn3-94
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.4086
• 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	None	None	0.032	N	0.475	0.142	0.354183961838	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.232	likely_benign	0.2072	benign	-1.933	Destabilizing	0.754	D	0.547	neutral	None	None	None	None	N
Y/C	0.0909	likely_benign	0.0899	benign	-0.771	Destabilizing	0.032	N	0.475	neutral	N	0.492929783	None	None	N
Y/D	0.1992	likely_benign	0.1654	benign	-0.56	Destabilizing	0.99	D	0.705	prob.neutral	N	0.49223635	None	None	N
Y/E	0.3512	ambiguous	0.3089	benign	-0.453	Destabilizing	0.993	D	0.698	prob.neutral	None	None	None	None	N
Y/F	0.0677	likely_benign	0.069	benign	-0.562	Destabilizing	0.014	N	0.479	neutral	N	0.423280484	None	None	N
Y/G	0.3121	likely_benign	0.2738	benign	-2.252	Highly Destabilizing	0.978	D	0.636	neutral	None	None	None	None	N
Y/H	0.1007	likely_benign	0.0871	benign	-0.542	Destabilizing	0.99	D	0.653	neutral	N	0.427859584	None	None	N
Y/I	0.2432	likely_benign	0.2092	benign	-0.965	Destabilizing	0.915	D	0.638	neutral	None	None	None	None	N
Y/K	0.4327	ambiguous	0.3576	ambiguous	-0.988	Destabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
Y/L	0.3337	likely_benign	0.2804	benign	-0.965	Destabilizing	0.754	D	0.543	neutral	None	None	None	None	N
Y/M	0.3853	ambiguous	0.3567	ambiguous	-0.722	Destabilizing	0.994	D	0.687	prob.neutral	None	None	None	None	N
Y/N	0.1017	likely_benign	0.0839	benign	-1.447	Destabilizing	0.99	D	0.701	prob.neutral	N	0.422587051	None	None	N
Y/P	0.9601	likely_pathogenic	0.9366	pathogenic	-1.283	Destabilizing	0.993	D	0.709	prob.delet.	None	None	None	None	N
Y/Q	0.2525	likely_benign	0.2091	benign	-1.309	Destabilizing	0.993	D	0.701	prob.neutral	None	None	None	None	N
Y/R	0.2643	likely_benign	0.2098	benign	-0.615	Destabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	N
Y/S	0.0953	likely_benign	0.083	benign	-1.972	Destabilizing	0.942	D	0.615	neutral	N	0.400091406	None	None	N
Y/T	0.1688	likely_benign	0.1491	benign	-1.77	Destabilizing	0.956	D	0.617	neutral	None	None	None	None	N
Y/V	0.1831	likely_benign	0.1614	benign	-1.283	Destabilizing	0.86	D	0.587	neutral	None	None	None	None	N
Y/W	0.2973	likely_benign	0.2784	benign	-0.132	Destabilizing	0.998	D	0.651	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.