TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14631	44116;44117;44118	chr2:178631157;178631156;178631155	chr2:179495884;179495883;179495882
N2AB	12990	39193;39194;39195	chr2:178631157;178631156;178631155	chr2:179495884;179495883;179495882
N2A	12063	36412;36413;36414	chr2:178631157;178631156;178631155	chr2:179495884;179495883;179495882
N2B	5566	16921;16922;16923	chr2:178631157;178631156;178631155	chr2:179495884;179495883;179495882
Novex-1	5691	17296;17297;17298	chr2:178631157;178631156;178631155	chr2:179495884;179495883;179495882
Novex-2	5758	17497;17498;17499	chr2:178631157;178631156;178631155	chr2:179495884;179495883;179495882
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-97
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.1933
• 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
A/T	None	None	0.012	N	0.521	0.082	0.306695030598	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
A/V	rs1237863283	None	None	N	0.181	0.183	0.0920862733494	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/V	rs1237863283	None	None	N	0.181	0.183	0.0920862733494	gnomAD-4.0.0	1.23982E-06	None	None	None	None	N	None	1.33561E-05	0	None	0	0	None	0	0	8.47759E-07	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
A/C	0.438	ambiguous	0.4446	ambiguous	-1.029	Destabilizing	0.001	N	0.383	neutral	None	None	None	None	N
A/D	0.4286	ambiguous	0.4002	ambiguous	-1.397	Destabilizing	0.295	N	0.669	neutral	N	0.495859179	None	None	N
A/E	0.3321	likely_benign	0.3092	benign	-1.366	Destabilizing	0.136	N	0.646	neutral	None	None	None	None	N
A/F	0.2752	likely_benign	0.2612	benign	-0.965	Destabilizing	0.214	N	0.667	neutral	None	None	None	None	N
A/G	0.2161	likely_benign	0.2144	benign	-1.351	Destabilizing	0.106	N	0.553	neutral	N	0.487577059	None	None	N
A/H	0.5663	likely_pathogenic	0.5483	ambiguous	-1.65	Destabilizing	0.864	D	0.622	neutral	None	None	None	None	N
A/I	0.1445	likely_benign	0.1348	benign	-0.226	Destabilizing	None	N	0.344	neutral	None	None	None	None	N
A/K	0.5242	ambiguous	0.5055	ambiguous	-1.338	Destabilizing	0.136	N	0.643	neutral	None	None	None	None	N
A/L	0.1745	likely_benign	0.1719	benign	-0.226	Destabilizing	0.007	N	0.44	neutral	None	None	None	None	N
A/M	0.1933	likely_benign	0.1793	benign	-0.21	Destabilizing	0.214	N	0.678	prob.neutral	None	None	None	None	N
A/N	0.35	ambiguous	0.3274	benign	-1.158	Destabilizing	0.628	D	0.661	neutral	None	None	None	None	N
A/P	0.7351	likely_pathogenic	0.757	pathogenic	-0.446	Destabilizing	0.295	N	0.681	prob.neutral	N	0.469136222	None	None	N
A/Q	0.4511	ambiguous	0.4326	ambiguous	-1.208	Destabilizing	0.628	D	0.679	prob.neutral	None	None	None	None	N
A/R	0.4531	ambiguous	0.4281	ambiguous	-1.127	Destabilizing	0.356	N	0.673	neutral	None	None	None	None	N
A/S	0.1178	likely_benign	0.114	benign	-1.572	Destabilizing	0.055	N	0.539	neutral	N	0.455436738	None	None	N
A/T	0.0856	likely_benign	0.0792	benign	-1.432	Destabilizing	0.012	N	0.521	neutral	N	0.441900416	None	None	N
A/V	0.078	likely_benign	0.0755	benign	-0.446	Destabilizing	None	N	0.181	neutral	N	0.306764423	None	None	N
A/W	0.7445	likely_pathogenic	0.74	pathogenic	-1.436	Destabilizing	0.864	D	0.669	neutral	None	None	None	None	N
A/Y	0.4385	ambiguous	0.4386	ambiguous	-0.989	Destabilizing	0.356	N	0.663	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.