TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2610	8053;8054;8055	chr2:178773136;178773135;178773134	chr2:179637863;179637862;179637861
N2AB	2610	8053;8054;8055	chr2:178773136;178773135;178773134	chr2:179637863;179637862;179637861
N2A	2610	8053;8054;8055	chr2:178773136;178773135;178773134	chr2:179637863;179637862;179637861
N2B	2564	7915;7916;7917	chr2:178773136;178773135;178773134	chr2:179637863;179637862;179637861
Novex-1	2564	7915;7916;7917	chr2:178773136;178773135;178773134	chr2:179637863;179637862;179637861
Novex-2	2564	7915;7916;7917	chr2:178773136;178773135;178773134	chr2:179637863;179637862;179637861
Novex-3	2610	8053;8054;8055	chr2:178773136;178773135;178773134	chr2:179637863;179637862;179637861

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-15
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.5391
• 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
M/I	rs56142888	0.31	None	N	0.117	0.104	0.337135696972	gnomAD-2.1.1	7.52578E-02	None	None	None	None	N	None	1.12942E-02	2.37808E-01	None	4.85615E-02	2.00322E-01	None	1.84338E-02	None	5.3183E-02	4.43085E-02	6.37023E-02
M/I	rs56142888	0.31	None	N	0.117	0.104	0.337135696972	gnomAD-3.1.2	4.98239E-02	None	None	None	None	N	None	1.16027E-02	1.37979E-01	4.82456E-02	4.89631E-02	1.83725E-01	None	5.13014E-02	1.58228E-02	4.51805E-02	2.2144E-02	4.63228E-02
M/I	rs56142888	0.31	None	N	0.117	0.104	0.337135696972	1000 genomes	7.54792E-02	None	None	None	None	N	None	2.3E-03	1.715E-01	None	None	1.905E-01	4.87E-02	None	None	None	1.53E-02	None
M/I	rs56142888	0.31	None	N	0.117	0.104	0.337135696972	gnomAD-4.0.0	5.24191E-02	None	None	None	None	N	None	1.05929E-02	2.0473E-01	None	4.7537E-02	1.88716E-01	None	5.40401E-02	1.6177E-02	4.49715E-02	1.97689E-02	5.11713E-02
M/L	None	None	0.001	N	0.125	0.11	0.32980341726	gnomAD-4.0.0	6.84169E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99361E-07	0	0
M/V	rs1331698925	0.143	None	N	0.121	0.085	0.363944505237	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.83E-06	0
M/V	rs1331698925	0.143	None	N	0.121	0.085	0.363944505237	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
M/V	rs1331698925	0.143	None	N	0.121	0.085	0.363944505237	gnomAD-4.0.0	1.85878E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.47509E-07	1.09815E-05	1.60005E-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
M/A	0.1831	likely_benign	0.2157	benign	-0.881	Destabilizing	0.002	N	0.225	neutral	None	None	None	None	N
M/C	0.4444	ambiguous	0.4019	ambiguous	-0.682	Destabilizing	0.245	N	0.47	neutral	None	None	None	None	N
M/D	0.6196	likely_pathogenic	0.6627	pathogenic	0.624	Stabilizing	0.018	N	0.378	neutral	None	None	None	None	N
M/E	0.1719	likely_benign	0.194	benign	0.645	Stabilizing	0.004	N	0.273	neutral	None	None	None	None	N
M/F	0.2888	likely_benign	0.2732	benign	-0.065	Destabilizing	0.085	N	0.45	neutral	None	None	None	None	N
M/G	0.4317	ambiguous	0.4467	ambiguous	-1.163	Destabilizing	0.008	N	0.299	neutral	None	None	None	None	N
M/H	0.2642	likely_benign	0.2871	benign	-0.213	Destabilizing	None	N	0.25	neutral	None	None	None	None	N
M/I	0.1965	likely_benign	0.2176	benign	-0.191	Destabilizing	None	N	0.117	neutral	N	0.413236192	None	None	N
M/K	0.0645	likely_benign	0.0807	benign	0.295	Stabilizing	None	N	0.171	neutral	N	0.308536078	None	None	N
M/L	0.1339	likely_benign	0.1534	benign	-0.191	Destabilizing	0.001	N	0.125	neutral	N	0.420710628	None	None	N
M/N	0.2929	likely_benign	0.3361	benign	0.357	Stabilizing	0.018	N	0.313	neutral	None	None	None	None	N
M/P	0.8675	likely_pathogenic	0.9127	pathogenic	-0.391	Destabilizing	0.037	N	0.485	neutral	None	None	None	None	N
M/Q	0.096	likely_benign	0.1041	benign	0.335	Stabilizing	0.018	N	0.421	neutral	None	None	None	None	N
M/R	0.0838	likely_benign	0.1023	benign	0.629	Stabilizing	None	N	0.184	neutral	N	0.392547113	None	None	N
M/S	0.1829	likely_benign	0.1994	benign	-0.283	Destabilizing	0.004	N	0.242	neutral	None	None	None	None	N
M/T	0.0877	likely_benign	0.1143	benign	-0.136	Destabilizing	None	N	0.171	neutral	N	0.319042843	None	None	N
M/V	0.0705	likely_benign	0.0807	benign	-0.391	Destabilizing	None	N	0.121	neutral	N	0.420710628	None	None	N
M/W	0.5617	ambiguous	0.551	ambiguous	-0.036	Destabilizing	0.497	N	0.467	neutral	None	None	None	None	N
M/Y	0.4055	ambiguous	0.4068	ambiguous	0.051	Stabilizing	0.044	N	0.533	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.