TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29392	88399;88400;88401	chr2:178556980;178556979;178556978	chr2:179421707;179421706;179421705
N2AB	27751	83476;83477;83478	chr2:178556980;178556979;178556978	chr2:179421707;179421706;179421705
N2A	26824	80695;80696;80697	chr2:178556980;178556979;178556978	chr2:179421707;179421706;179421705
N2B	20327	61204;61205;61206	chr2:178556980;178556979;178556978	chr2:179421707;179421706;179421705
Novex-1	20452	61579;61580;61581	chr2:178556980;178556979;178556978	chr2:179421707;179421706;179421705
Novex-2	20519	61780;61781;61782	chr2:178556980;178556979;178556978	chr2:179421707;179421706;179421705
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-102
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.5439
• Predicted PPI site: I

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
E/K	rs1553551691	None	0.978	N	0.533	0.351	0.338834610459	gnomAD-4.0.0	3.18261E-06	None	None	None	None	I	None	5.65291E-05	0	None	0	0	None	0	0	2.85799E-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
E/A	0.2164	likely_benign	0.173	benign	-0.291	Destabilizing	0.989	D	0.601	neutral	N	0.504242855	None	None	I
E/C	0.9184	likely_pathogenic	0.8964	pathogenic	-0.279	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
E/D	0.0896	likely_benign	0.0905	benign	-0.519	Destabilizing	0.054	N	0.166	neutral	N	0.413122205	None	None	I
E/F	0.923	likely_pathogenic	0.8905	pathogenic	0.127	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	I
E/G	0.1856	likely_benign	0.1513	benign	-0.536	Destabilizing	0.978	D	0.55	neutral	N	0.470650356	None	None	I
E/H	0.5909	likely_pathogenic	0.5337	ambiguous	0.522	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	I
E/I	0.682	likely_pathogenic	0.5998	pathogenic	0.338	Stabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
E/K	0.2127	likely_benign	0.1738	benign	0.286	Stabilizing	0.978	D	0.533	neutral	N	0.489620119	None	None	I
E/L	0.6931	likely_pathogenic	0.6092	pathogenic	0.338	Stabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	I
E/M	0.6849	likely_pathogenic	0.6068	pathogenic	0.222	Stabilizing	1.0	D	0.656	neutral	None	None	None	None	I
E/N	0.2338	likely_benign	0.2023	benign	-0.303	Destabilizing	0.995	D	0.601	neutral	None	None	None	None	I
E/P	0.8953	likely_pathogenic	0.8664	pathogenic	0.149	Stabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
E/Q	0.1991	likely_benign	0.1721	benign	-0.21	Destabilizing	0.997	D	0.586	neutral	N	0.505493649	None	None	I
E/R	0.3884	ambiguous	0.3313	benign	0.669	Stabilizing	0.998	D	0.645	neutral	None	None	None	None	I
E/S	0.223	likely_benign	0.1862	benign	-0.441	Destabilizing	0.983	D	0.539	neutral	None	None	None	None	I
E/T	0.3014	likely_benign	0.2441	benign	-0.225	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	I
E/V	0.4333	ambiguous	0.362	ambiguous	0.149	Stabilizing	0.999	D	0.684	prob.neutral	N	0.516076002	None	None	I
E/W	0.9717	likely_pathogenic	0.958	pathogenic	0.345	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
E/Y	0.811	likely_pathogenic	0.7515	pathogenic	0.399	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I

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.