TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29424	88495;88496;88497	chr2:178556884;178556883;178556882	chr2:179421611;179421610;179421609
N2AB	27783	83572;83573;83574	chr2:178556884;178556883;178556882	chr2:179421611;179421610;179421609
N2A	26856	80791;80792;80793	chr2:178556884;178556883;178556882	chr2:179421611;179421610;179421609
N2B	20359	61300;61301;61302	chr2:178556884;178556883;178556882	chr2:179421611;179421610;179421609
Novex-1	20484	61675;61676;61677	chr2:178556884;178556883;178556882	chr2:179421611;179421610;179421609
Novex-2	20551	61876;61877;61878	chr2:178556884;178556883;178556882	chr2:179421611;179421610;179421609
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-102
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.3198
• 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/D	rs9808036	None	0.002	N	0.23	0.048	0.0920862733494	gnomAD-4.0.0	3.42122E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49724E-06	0	0
E/K	None	None	0.651	N	0.404	0.227	0.210429274316	gnomAD-4.0.0	3.18278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71598E-06	0	0
E/Q	rs763574979	-0.67	0.791	N	0.42	0.128	0.206339911435	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/Q	rs763574979	-0.67	0.791	N	0.42	0.128	0.206339911435	gnomAD-4.0.0	1.59139E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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	0.1467	likely_benign	0.1409	benign	-0.11	Destabilizing	0.435	N	0.483	neutral	N	0.494785505	None	None	N
E/C	0.797	likely_pathogenic	0.7978	pathogenic	-0.092	Destabilizing	0.995	D	0.631	neutral	None	None	None	None	N
E/D	0.0807	likely_benign	0.0898	benign	-0.289	Destabilizing	0.002	N	0.23	neutral	N	0.439238866	None	None	N
E/F	0.7633	likely_pathogenic	0.7147	pathogenic	-0.014	Destabilizing	0.897	D	0.623	neutral	None	None	None	None	N
E/G	0.1977	likely_benign	0.1843	benign	-0.269	Destabilizing	0.651	D	0.559	neutral	N	0.46339157	None	None	N
E/H	0.4385	ambiguous	0.4231	ambiguous	0.435	Stabilizing	0.982	D	0.417	neutral	None	None	None	None	N
E/I	0.3787	ambiguous	0.3358	benign	0.263	Stabilizing	0.032	N	0.569	neutral	None	None	None	None	N
E/K	0.1737	likely_benign	0.1506	benign	0.501	Stabilizing	0.651	D	0.404	neutral	N	0.50025004	None	None	N
E/L	0.3847	ambiguous	0.3532	ambiguous	0.263	Stabilizing	0.338	N	0.543	neutral	None	None	None	None	N
E/M	0.4682	ambiguous	0.4238	ambiguous	0.127	Stabilizing	0.088	N	0.524	neutral	None	None	None	None	N
E/N	0.1934	likely_benign	0.1975	benign	0.127	Stabilizing	0.553	D	0.379	neutral	None	None	None	None	N
E/P	0.369	ambiguous	0.3913	ambiguous	0.158	Stabilizing	0.946	D	0.537	neutral	None	None	None	None	N
E/Q	0.1702	likely_benign	0.1604	benign	0.165	Stabilizing	0.791	D	0.42	neutral	N	0.496825732	None	None	N
E/R	0.2841	likely_benign	0.2563	benign	0.719	Stabilizing	0.946	D	0.383	neutral	None	None	None	None	N
E/S	0.1753	likely_benign	0.1778	benign	0.013	Stabilizing	0.712	D	0.415	neutral	None	None	None	None	N
E/T	0.2267	likely_benign	0.2167	benign	0.152	Stabilizing	0.712	D	0.483	neutral	None	None	None	None	N
E/V	0.2195	likely_benign	0.1953	benign	0.158	Stabilizing	0.278	N	0.535	neutral	N	0.461443013	None	None	N
E/W	0.8994	likely_pathogenic	0.8754	pathogenic	0.093	Stabilizing	0.995	D	0.651	prob.neutral	None	None	None	None	N
E/Y	0.5959	likely_pathogenic	0.5631	ambiguous	0.228	Stabilizing	0.982	D	0.623	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.