TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18701	56326;56327;56328	chr2:178599800;178599799;178599798	chr2:179464527;179464526;179464525
N2AB	17060	51403;51404;51405	chr2:178599800;178599799;178599798	chr2:179464527;179464526;179464525
N2A	16133	48622;48623;48624	chr2:178599800;178599799;178599798	chr2:179464527;179464526;179464525
N2B	9636	29131;29132;29133	chr2:178599800;178599799;178599798	chr2:179464527;179464526;179464525
Novex-1	9761	29506;29507;29508	chr2:178599800;178599799;178599798	chr2:179464527;179464526;179464525
Novex-2	9828	29707;29708;29709	chr2:178599800;178599799;178599798	chr2:179464527;179464526;179464525
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-116
• Domain position: 14
• Structural Position: 26
• Q(SASA): 0.5652
• 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
N/D	rs1001238	0.171	None	N	0.1	0.162	None	gnomAD-2.1.1	3.54674E-01	None	None	None	None	N	None	5.41211E-01	4.31485E-01	None	2.88348E-01	7.1154E-01	None	5.22932E-01	None	2.77491E-01	2.27833E-01	3.10017E-01
N/D	rs1001238	0.171	None	N	0.1	0.162	None	gnomAD-3.1.2	3.631E-01	None	None	None	None	N	None	5.40248E-01	3.87211E-01	5.59341E-01	2.90611E-01	7.08757E-01	None	2.87323E-01	2.81646E-01	2.27012E-01	5.20747E-01	3.30932E-01
N/D	rs1001238	0.171	None	N	0.1	0.162	None	1000 genomes	5.1278E-01	None	None	None	None	N	None	5.688E-01	4.078E-01	None	None	7.252E-01	2.535E-01	None	None	None	5.593E-01	None
N/D	rs1001238	0.171	None	N	0.1	0.162	None	gnomAD-4.0.0	2.78915E-01	None	None	None	None	N	None	5.4686E-01	4.18557E-01	None	2.88409E-01	7.02305E-01	None	2.80055E-01	3.15589E-01	2.19149E-01	5.10058E-01	3.06389E-01
N/I	None	None	0.006	N	0.33	0.203	0.377976839388	gnomAD-4.0.0	6.86502E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66279E-05
N/S	rs917862808	None	None	N	0.165	0.2	0.0611884634855	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
N/S	rs917862808	None	None	N	0.165	0.2	0.0611884634855	gnomAD-4.0.0	1.24324E-06	None	None	None	None	N	None	0	1.68885E-05	None	0	0	None	0	0	0	0	1.60694E-05

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
N/A	0.1456	likely_benign	0.1374	benign	-0.435	Destabilizing	0.001	N	0.196	neutral	None	None	None	None	N
N/C	0.2887	likely_benign	0.2954	benign	0.378	Stabilizing	0.316	N	0.461	neutral	None	None	None	None	N
N/D	0.0583	likely_benign	0.0524	benign	-0.324	Destabilizing	None	N	0.1	neutral	N	0.380747923	None	None	N
N/E	0.1998	likely_benign	0.1843	benign	-0.332	Destabilizing	None	N	0.106	neutral	None	None	None	None	N
N/F	0.5053	ambiguous	0.4818	ambiguous	-0.675	Destabilizing	0.051	N	0.357	neutral	None	None	None	None	N
N/G	0.2435	likely_benign	0.2113	benign	-0.659	Destabilizing	None	N	0.155	neutral	None	None	None	None	N
N/H	0.1429	likely_benign	0.1452	benign	-0.745	Destabilizing	0.013	N	0.283	neutral	N	0.479874767	None	None	N
N/I	0.2136	likely_benign	0.2235	benign	0.081	Stabilizing	0.006	N	0.33	neutral	N	0.506271935	None	None	N
N/K	0.2852	likely_benign	0.2939	benign	-0.013	Destabilizing	0.001	N	0.186	neutral	N	0.451456015	None	None	N
N/L	0.2478	likely_benign	0.2502	benign	0.081	Stabilizing	0.002	N	0.335	neutral	None	None	None	None	N
N/M	0.3485	ambiguous	0.3406	ambiguous	0.651	Stabilizing	0.116	N	0.45	neutral	None	None	None	None	N
N/P	0.3538	ambiguous	0.3492	ambiguous	-0.063	Destabilizing	0.003	N	0.283	neutral	None	None	None	None	N
N/Q	0.2893	likely_benign	0.2768	benign	-0.588	Destabilizing	0.002	N	0.201	neutral	None	None	None	None	N
N/R	0.3191	likely_benign	0.3183	benign	0.05	Stabilizing	0.002	N	0.235	neutral	None	None	None	None	N
N/S	0.0784	likely_benign	0.075	benign	-0.313	Destabilizing	None	N	0.165	neutral	N	0.390655485	None	None	N
N/T	0.1128	likely_benign	0.1127	benign	-0.17	Destabilizing	0.001	N	0.183	neutral	N	0.402949992	None	None	N
N/V	0.1756	likely_benign	0.1735	benign	-0.063	Destabilizing	0.003	N	0.318	neutral	None	None	None	None	N
N/W	0.7646	likely_pathogenic	0.7417	pathogenic	-0.588	Destabilizing	0.316	N	0.375	neutral	None	None	None	None	N
N/Y	0.1637	likely_benign	0.1683	benign	-0.338	Destabilizing	0.039	N	0.347	neutral	N	0.498903245	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.