TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31838	95737;95738;95739	chr2:178545598;178545597;178545596	chr2:179410325;179410324;179410323
N2AB	30197	90814;90815;90816	chr2:178545598;178545597;178545596	chr2:179410325;179410324;179410323
N2A	29270	88033;88034;88035	chr2:178545598;178545597;178545596	chr2:179410325;179410324;179410323
N2B	22773	68542;68543;68544	chr2:178545598;178545597;178545596	chr2:179410325;179410324;179410323
Novex-1	22898	68917;68918;68919	chr2:178545598;178545597;178545596	chr2:179410325;179410324;179410323
Novex-2	22965	69118;69119;69120	chr2:178545598;178545597;178545596	chr2:179410325;179410324;179410323
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: Fn3-120
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.5817
• 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/G	rs1196738790	-0.438	0.83	N	0.657	0.309	0.366277470483	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65508E-04
E/G	rs1196738790	-0.438	0.83	N	0.657	0.309	0.366277470483	gnomAD-4.0.0	2.73693E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69854E-06	0	1.65684E-05
E/V	None	None	0.908	N	0.707	0.392	0.363944505237	gnomAD-4.0.0	1.36847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79902E-06	0	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	0.1721	likely_benign	0.1537	benign	-0.186	Destabilizing	0.581	D	0.625	neutral	N	0.515499999	None	None	N
E/C	0.809	likely_pathogenic	0.7565	pathogenic	0.037	Stabilizing	0.993	D	0.699	prob.neutral	None	None	None	None	N
E/D	0.0912	likely_benign	0.0789	benign	-0.208	Destabilizing	0.004	N	0.191	neutral	N	0.505283005	None	None	N
E/F	0.8031	likely_pathogenic	0.7391	pathogenic	-0.208	Destabilizing	0.993	D	0.677	prob.neutral	None	None	None	None	N
E/G	0.2378	likely_benign	0.1914	benign	-0.337	Destabilizing	0.83	D	0.657	neutral	N	0.485362117	None	None	N
E/H	0.5366	ambiguous	0.4757	ambiguous	0.172	Stabilizing	0.98	D	0.724	prob.delet.	None	None	None	None	N
E/I	0.3817	ambiguous	0.333	benign	0.162	Stabilizing	0.929	D	0.7	prob.neutral	None	None	None	None	N
E/K	0.2152	likely_benign	0.1817	benign	0.455	Stabilizing	0.581	D	0.592	neutral	N	0.489121474	None	None	N
E/L	0.448	ambiguous	0.3958	ambiguous	0.162	Stabilizing	0.866	D	0.694	prob.neutral	None	None	None	None	N
E/M	0.4976	ambiguous	0.4415	ambiguous	0.162	Stabilizing	0.993	D	0.674	neutral	None	None	None	None	N
E/N	0.2461	likely_benign	0.1947	benign	0.253	Stabilizing	0.764	D	0.738	prob.delet.	None	None	None	None	N
E/P	0.3105	likely_benign	0.3189	benign	0.065	Stabilizing	0.929	D	0.715	prob.delet.	None	None	None	None	N
E/Q	0.197	likely_benign	0.1737	benign	0.264	Stabilizing	0.83	D	0.671	neutral	N	0.479081467	None	None	N
E/R	0.3505	ambiguous	0.3077	benign	0.632	Stabilizing	0.866	D	0.756	deleterious	None	None	None	None	N
E/S	0.2189	likely_benign	0.1856	benign	0.083	Stabilizing	0.48	N	0.63	neutral	None	None	None	None	N
E/T	0.2466	likely_benign	0.2118	benign	0.208	Stabilizing	0.866	D	0.685	prob.neutral	None	None	None	None	N
E/V	0.2396	likely_benign	0.2096	benign	0.065	Stabilizing	0.908	D	0.707	prob.neutral	N	0.492337103	None	None	N
E/W	0.9233	likely_pathogenic	0.8892	pathogenic	-0.124	Destabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
E/Y	0.6673	likely_pathogenic	0.5726	pathogenic	0.027	Stabilizing	0.993	D	0.699	prob.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.