TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8144	24655;24656;24657	chr2:178718770;178718769;178718768	chr2:179583497;179583496;179583495
N2AB	7827	23704;23705;23706	chr2:178718770;178718769;178718768	chr2:179583497;179583496;179583495
N2A	6900	20923;20924;20925	chr2:178718770;178718769;178718768	chr2:179583497;179583496;179583495
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-66
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.2502
• 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/A	rs16866465	1.123	0.003	N	0.449	0.227	None	gnomAD-2.1.1	1.75062E-01	None	None	None	None	N	None	1.52217E-01	1.7377E-01	None	1.22413E-01	4.30462E-01	None	2.22538E-01	None	9.45222E-02	1.50195E-01	1.61608E-01
E/A	rs16866465	1.123	0.003	N	0.449	0.227	None	gnomAD-3.1.2	1.64715E-01	None	None	None	None	N	None	1.5358E-01	1.70055E-01	4.71491E-01	1.25864E-01	4.33191E-01	None	9.86805E-02	1.20253E-01	1.54076E-01	2.23766E-01	1.65392E-01
E/A	rs16866465	1.123	0.003	N	0.449	0.227	None	1000 genomes	2.38818E-01	None	None	None	None	N	None	1.732E-01	1.83E-01	None	None	4.375E-01	1.571E-01	None	None	None	2.464E-01	None
E/A	rs16866465	1.123	0.003	N	0.449	0.227	None	gnomAD-4.0.0	1.63466E-01	None	None	None	None	N	None	1.53334E-01	1.73385E-01	None	1.23767E-01	4.42663E-01	None	9.43438E-02	1.92079E-01	1.52621E-01	2.20242E-01	1.70103E-01
E/D	rs756559627	-1.13	0.003	N	0.431	0.034	0.0297737177859	gnomAD-2.1.1	1.17847E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.39754E-04	1.56365E-04	2.80662E-04
E/D	rs756559627	-1.13	0.003	N	0.431	0.034	0.0297737177859	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	0	0	0	0	0	None	1.88395E-04	0	5.88E-05	0	0
E/D	rs756559627	-1.13	0.003	N	0.431	0.034	0.0297737177859	gnomAD-4.0.0	1.14028E-04	None	None	None	None	N	None	0	0	None	0	0	None	5.4679E-04	0	1.16127E-04	0	1.92111E-04
E/G	rs16866465	0.345	0.007	N	0.539	0.234	0.388812400583	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	1.11408E-04	None	0	None	0	0	0
E/G	rs16866465	0.345	0.007	N	0.539	0.234	0.388812400583	gnomAD-4.0.0	2.73688E-06	None	None	None	None	N	None	0	0	None	0	7.55896E-05	None	0	0	0	0	1.65667E-05
E/K	rs761751961	1.065	0.003	N	0.449	0.16	0.204665344411	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs761751961	1.065	0.003	N	0.449	0.16	0.204665344411	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
E/K	rs761751961	1.065	0.003	N	0.449	0.16	0.204665344411	gnomAD-4.0.0	5.12449E-06	None	None	None	None	N	None	0	0	None	0	2.42483E-05	None	0	0	0	4.02026E-05	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	0.1376	likely_benign	0.1516	benign	0.09	Stabilizing	0.003	N	0.449	neutral	N	0.474896675	None	None	N
E/C	0.6673	likely_pathogenic	0.6348	pathogenic	0.062	Stabilizing	0.788	D	0.695	prob.neutral	None	None	None	None	N
E/D	0.1379	likely_benign	0.1326	benign	-1.122	Destabilizing	0.003	N	0.431	neutral	N	0.298556188	None	None	N
E/F	0.5284	ambiguous	0.5215	ambiguous	0.989	Stabilizing	None	N	0.459	neutral	None	None	None	None	N
E/G	0.1502	likely_benign	0.1485	benign	-0.358	Destabilizing	0.007	N	0.539	neutral	N	0.474896675	None	None	N
E/H	0.1717	likely_benign	0.1661	benign	0.811	Stabilizing	None	N	0.222	neutral	None	None	None	None	N
E/I	0.3162	likely_benign	0.3159	benign	1.321	Stabilizing	0.044	N	0.67	neutral	None	None	None	None	N
E/K	0.1233	likely_benign	0.1249	benign	0.161	Stabilizing	0.003	N	0.449	neutral	N	0.46691191	None	None	N
E/L	0.175	likely_benign	0.1641	benign	1.321	Stabilizing	0.009	N	0.567	neutral	None	None	None	None	N
E/M	0.3418	ambiguous	0.3265	benign	1.579	Stabilizing	0.245	N	0.698	prob.neutral	None	None	None	None	N
E/N	0.1929	likely_benign	0.1846	benign	-0.795	Destabilizing	None	N	0.227	neutral	None	None	None	None	N
E/P	0.3916	ambiguous	0.3546	ambiguous	0.935	Stabilizing	0.085	N	0.569	neutral	None	None	None	None	N
E/Q	0.0622	likely_benign	0.0642	benign	-0.488	Destabilizing	None	N	0.207	neutral	N	0.358725652	None	None	N
E/R	0.1505	likely_benign	0.1549	benign	0.351	Stabilizing	0.009	N	0.468	neutral	None	None	None	None	N
E/S	0.1812	likely_benign	0.1775	benign	-1.035	Destabilizing	0.004	N	0.447	neutral	None	None	None	None	N
E/T	0.2208	likely_benign	0.22	benign	-0.616	Destabilizing	0.018	N	0.502	neutral	None	None	None	None	N
E/V	0.1981	likely_benign	0.1953	benign	0.935	Stabilizing	0.014	N	0.59	neutral	N	0.504872865	None	None	N
E/W	0.6548	likely_pathogenic	0.6362	pathogenic	1.187	Stabilizing	0.788	D	0.696	prob.neutral	None	None	None	None	N
E/Y	0.3495	ambiguous	0.3331	benign	1.295	Stabilizing	0.009	N	0.596	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.