TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8786	26581;26582;26583	chr2:178714418;178714417;178714416	chr2:179579145;179579144;179579143
N2AB	8469	25630;25631;25632	chr2:178714418;178714417;178714416	chr2:179579145;179579144;179579143
N2A	7542	22849;22850;22851	chr2:178714418;178714417;178714416	chr2:179579145;179579144;179579143
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-73
• Domain position: 51
• Structural Position: 125
• Q(SASA): 0.3621
• 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
S/A	None	None	0.308	N	0.399	0.172	0.263140351381	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0869	likely_benign	0.0989	benign	-0.702	Destabilizing	0.308	N	0.399	neutral	N	0.488668524	None	None	N
S/C	0.1538	likely_benign	0.1973	benign	-0.382	Destabilizing	0.999	D	0.613	neutral	D	0.532273775	None	None	N
S/D	0.3688	ambiguous	0.4415	ambiguous	0.074	Stabilizing	0.975	D	0.455	neutral	None	None	None	None	N
S/E	0.477	ambiguous	0.5402	ambiguous	0.084	Stabilizing	0.982	D	0.443	neutral	None	None	None	None	N
S/F	0.1573	likely_benign	0.1948	benign	-0.88	Destabilizing	0.999	D	0.715	prob.delet.	N	0.505522239	None	None	N
S/G	0.1108	likely_benign	0.1312	benign	-0.961	Destabilizing	0.986	D	0.501	neutral	None	None	None	None	N
S/H	0.2846	likely_benign	0.3119	benign	-1.355	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
S/I	0.1619	likely_benign	0.2104	benign	-0.119	Destabilizing	0.996	D	0.645	neutral	None	None	None	None	N
S/K	0.54	ambiguous	0.5987	pathogenic	-0.536	Destabilizing	0.986	D	0.444	neutral	None	None	None	None	N
S/L	0.0999	likely_benign	0.1199	benign	-0.119	Destabilizing	0.986	D	0.587	neutral	None	None	None	None	N
S/M	0.2112	likely_benign	0.2474	benign	0.047	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
S/N	0.1475	likely_benign	0.1797	benign	-0.498	Destabilizing	0.821	D	0.468	neutral	None	None	None	None	N
S/P	0.7344	likely_pathogenic	0.8709	pathogenic	-0.279	Destabilizing	0.997	D	0.557	neutral	N	0.513827125	None	None	N
S/Q	0.4372	ambiguous	0.4816	ambiguous	-0.573	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
S/R	0.4196	ambiguous	0.4706	ambiguous	-0.48	Destabilizing	0.998	D	0.581	neutral	None	None	None	None	N
S/T	0.0747	likely_benign	0.0838	benign	-0.526	Destabilizing	0.01	N	0.174	neutral	N	0.450094231	None	None	N
S/V	0.1789	likely_benign	0.2252	benign	-0.279	Destabilizing	0.964	D	0.588	neutral	None	None	None	None	N
S/W	0.2833	likely_benign	0.347	ambiguous	-0.879	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
S/Y	0.1527	likely_benign	0.1754	benign	-0.599	Destabilizing	0.999	D	0.72	prob.delet.	N	0.502559725	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.