TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5427	16504;16505;16506	chr2:178732897;178732896;178732895	chr2:179597624;179597623;179597622
N2AB	5110	15553;15554;15555	chr2:178732897;178732896;178732895	chr2:179597624;179597623;179597622
N2A	4183	12772;12773;12774	chr2:178732897;178732896;178732895	chr2:179597624;179597623;179597622
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-37
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1629
• 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
F/L	None	None	0.64	N	0.675	0.476	0.32714864917	gnomAD-4.0.0	1.59221E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-06	0	0
F/V	rs776697030	-1.695	0.896	N	0.769	0.445	0.620205906853	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
F/V	rs776697030	-1.695	0.896	N	0.769	0.445	0.620205906853	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
F/V	rs776697030	-1.695	0.896	N	0.769	0.445	0.620205906853	gnomAD-4.0.0	3.84521E-06	None	None	None	None	N	None	0	5.08837E-05	None	0	0	None	0	0	0	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
F/A	0.9735	likely_pathogenic	0.9812	pathogenic	-2.383	Highly Destabilizing	0.919	D	0.804	deleterious	None	None	None	None	N
F/C	0.8253	likely_pathogenic	0.8621	pathogenic	-2.146	Highly Destabilizing	0.999	D	0.875	deleterious	N	0.488470811	None	None	N
F/D	0.9975	likely_pathogenic	0.9983	pathogenic	-2.791	Highly Destabilizing	0.996	D	0.881	deleterious	None	None	None	None	N
F/E	0.9977	likely_pathogenic	0.9984	pathogenic	-2.553	Highly Destabilizing	0.988	D	0.866	deleterious	None	None	None	None	N
F/G	0.9911	likely_pathogenic	0.9935	pathogenic	-2.864	Highly Destabilizing	0.988	D	0.846	deleterious	None	None	None	None	N
F/H	0.956	likely_pathogenic	0.9641	pathogenic	-1.9	Destabilizing	0.976	D	0.811	deleterious	None	None	None	None	N
F/I	0.3749	ambiguous	0.4703	ambiguous	-0.82	Destabilizing	0.896	D	0.703	prob.neutral	N	0.505117142	None	None	N
F/K	0.9971	likely_pathogenic	0.9979	pathogenic	-1.99	Destabilizing	0.988	D	0.87	deleterious	None	None	None	None	N
F/L	0.9113	likely_pathogenic	0.943	pathogenic	-0.82	Destabilizing	0.64	D	0.675	prob.neutral	N	0.476607526	None	None	N
F/M	0.8239	likely_pathogenic	0.8704	pathogenic	-0.925	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
F/N	0.9878	likely_pathogenic	0.9917	pathogenic	-2.55	Highly Destabilizing	0.988	D	0.886	deleterious	None	None	None	None	N
F/P	0.9991	likely_pathogenic	0.9995	pathogenic	-1.353	Destabilizing	0.996	D	0.882	deleterious	None	None	None	None	N
F/Q	0.9951	likely_pathogenic	0.9963	pathogenic	-2.358	Highly Destabilizing	0.996	D	0.887	deleterious	None	None	None	None	N
F/R	0.99	likely_pathogenic	0.9924	pathogenic	-1.797	Destabilizing	0.988	D	0.887	deleterious	None	None	None	None	N
F/S	0.975	likely_pathogenic	0.9828	pathogenic	-3.217	Highly Destabilizing	0.984	D	0.823	deleterious	N	0.488470811	None	None	N
F/T	0.9676	likely_pathogenic	0.9777	pathogenic	-2.845	Highly Destabilizing	0.988	D	0.815	deleterious	None	None	None	None	N
F/V	0.4201	ambiguous	0.5028	ambiguous	-1.353	Destabilizing	0.896	D	0.769	deleterious	N	0.464997731	None	None	N
F/W	0.7441	likely_pathogenic	0.7786	pathogenic	-0.332	Destabilizing	0.988	D	0.689	prob.neutral	None	None	None	None	N
F/Y	0.154	likely_benign	0.1682	benign	-0.667	Destabilizing	0.004	N	0.354	neutral	N	0.308651233	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.