TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20759	62500;62501;62502	chr2:178589450;178589449;178589448	chr2:179454177;179454176;179454175
N2AB	19118	57577;57578;57579	chr2:178589450;178589449;178589448	chr2:179454177;179454176;179454175
N2A	18191	54796;54797;54798	chr2:178589450;178589449;178589448	chr2:179454177;179454176;179454175
N2B	11694	35305;35306;35307	chr2:178589450;178589449;178589448	chr2:179454177;179454176;179454175
Novex-1	11819	35680;35681;35682	chr2:178589450;178589449;178589448	chr2:179454177;179454176;179454175
Novex-2	11886	35881;35882;35883	chr2:178589450;178589449;178589448	chr2:179454177;179454176;179454175
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: Fn3-38
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.6686
• 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
E/K	rs562680371	0.736	0.842	N	0.422	0.217	0.313210971179	gnomAD-2.1.1	5.08061E-04	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	4.57696E-03	None	0	0	0
E/K	rs562680371	0.736	0.842	N	0.422	0.217	0.313210971179	gnomAD-3.1.2	2.23608E-04	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	6.63075E-03	4.78469E-04
E/K	rs562680371	0.736	0.842	N	0.422	0.217	0.313210971179	1000 genomes	1.19808E-03	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	6.1E-03	None
E/K	rs562680371	0.736	0.842	N	0.422	0.217	0.313210971179	gnomAD-4.0.0	2.64661E-04	None	None	None	None	N	None	2.66631E-05	0	None	0	0	None	0	1.6518E-04	8.47725E-07	4.44723E-03	2.88138E-04

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	0.1511	likely_benign	0.1411	benign	-0.638	Destabilizing	0.915	D	0.379	neutral	N	0.51405163	None	None	N
E/C	0.9033	likely_pathogenic	0.9069	pathogenic	-0.284	Destabilizing	0.998	D	0.568	neutral	None	None	None	None	N
E/D	0.1682	likely_benign	0.1701	benign	-0.68	Destabilizing	0.007	N	0.113	neutral	N	0.442999608	None	None	N
E/F	0.864	likely_pathogenic	0.8691	pathogenic	-0.284	Destabilizing	0.994	D	0.525	neutral	None	None	None	None	N
E/G	0.2954	likely_benign	0.2665	benign	-0.906	Destabilizing	0.842	D	0.439	neutral	N	0.514918422	None	None	N
E/H	0.7375	likely_pathogenic	0.7273	pathogenic	-0.237	Destabilizing	0.981	D	0.352	neutral	None	None	None	None	N
E/I	0.4582	ambiguous	0.4893	ambiguous	0.059	Stabilizing	0.994	D	0.577	neutral	None	None	None	None	N
E/K	0.3823	ambiguous	0.3733	ambiguous	-0.08	Destabilizing	0.842	D	0.422	neutral	N	0.509896604	None	None	N
E/L	0.5125	ambiguous	0.5298	ambiguous	0.059	Stabilizing	0.981	D	0.523	neutral	None	None	None	None	N
E/M	0.5168	ambiguous	0.538	ambiguous	0.241	Stabilizing	0.998	D	0.491	neutral	None	None	None	None	N
E/N	0.3481	ambiguous	0.3323	benign	-0.497	Destabilizing	0.038	N	0.1	neutral	None	None	None	None	N
E/P	0.4292	ambiguous	0.4	ambiguous	-0.152	Destabilizing	0.994	D	0.483	neutral	None	None	None	None	N
E/Q	0.2625	likely_benign	0.2465	benign	-0.429	Destabilizing	0.915	D	0.463	neutral	N	0.471996987	None	None	N
E/R	0.576	likely_pathogenic	0.5576	ambiguous	0.209	Stabilizing	0.981	D	0.394	neutral	None	None	None	None	N
E/S	0.2863	likely_benign	0.2596	benign	-0.689	Destabilizing	0.745	D	0.348	neutral	None	None	None	None	N
E/T	0.2674	likely_benign	0.244	benign	-0.471	Destabilizing	0.876	D	0.32	neutral	None	None	None	None	N
E/V	0.2687	likely_benign	0.2798	benign	-0.152	Destabilizing	0.991	D	0.5	neutral	N	0.470729539	None	None	N
E/W	0.9549	likely_pathogenic	0.9575	pathogenic	-0.047	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
E/Y	0.7833	likely_pathogenic	0.7958	pathogenic	-0.029	Destabilizing	0.994	D	0.518	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.