TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14428	43507;43508;43509	chr2:178632724;178632723;178632722	chr2:179497451;179497450;179497449
N2AB	12787	38584;38585;38586	chr2:178632724;178632723;178632722	chr2:179497451;179497450;179497449
N2A	11860	35803;35804;35805	chr2:178632724;178632723;178632722	chr2:179497451;179497450;179497449
N2B	5363	16312;16313;16314	chr2:178632724;178632723;178632722	chr2:179497451;179497450;179497449
Novex-1	5488	16687;16688;16689	chr2:178632724;178632723;178632722	chr2:179497451;179497450;179497449
Novex-2	5555	16888;16889;16890	chr2:178632724;178632723;178632722	chr2:179497451;179497450;179497449
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: Ig-95
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.3133
• 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	rs1261167534	-1.076	0.434	N	0.247	0.091	0.241078983079	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
E/D	rs1261167534	-1.076	0.434	N	0.247	0.091	0.241078983079	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1261167534	-1.076	0.434	N	0.247	0.091	0.241078983079	gnomAD-4.0.0	1.42569E-05	None	None	None	None	N	None	1.33497E-05	0	None	0	0	None	0	0	1.86509E-05	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	0.2068	likely_benign	0.2045	benign	-0.834	Destabilizing	0.998	D	0.662	neutral	D	0.613277725	None	None	N
E/C	0.8907	likely_pathogenic	0.8617	pathogenic	-0.376	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/D	0.3012	likely_benign	0.2442	benign	-1.023	Destabilizing	0.434	N	0.247	neutral	N	0.507460364	None	None	N
E/F	0.7925	likely_pathogenic	0.757	pathogenic	-0.422	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/G	0.3101	likely_benign	0.2957	benign	-1.168	Destabilizing	0.999	D	0.751	deleterious	D	0.656170643	None	None	N
E/H	0.5906	likely_pathogenic	0.5238	ambiguous	-0.656	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/I	0.3357	likely_benign	0.3285	benign	0.066	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/K	0.2317	likely_benign	0.2409	benign	-0.455	Destabilizing	0.998	D	0.57	neutral	N	0.508711952	None	None	N
E/L	0.5037	ambiguous	0.4812	ambiguous	0.066	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/M	0.5267	ambiguous	0.5005	ambiguous	0.494	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/N	0.4427	ambiguous	0.3968	ambiguous	-0.895	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
E/P	0.9627	likely_pathogenic	0.957	pathogenic	-0.213	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/Q	0.1649	likely_benign	0.1596	benign	-0.789	Destabilizing	0.999	D	0.685	prob.neutral	D	0.578957034	None	None	N
E/R	0.3715	ambiguous	0.3551	ambiguous	-0.212	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/S	0.2485	likely_benign	0.2256	benign	-1.164	Destabilizing	0.997	D	0.598	neutral	None	None	None	None	N
E/T	0.237	likely_benign	0.2204	benign	-0.889	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/V	0.2199	likely_benign	0.2085	benign	-0.213	Destabilizing	1.0	D	0.785	deleterious	D	0.576009236	None	None	N
E/W	0.9397	likely_pathogenic	0.9147	pathogenic	-0.187	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/Y	0.7427	likely_pathogenic	0.695	pathogenic	-0.172	Destabilizing	1.0	D	0.794	deleterious	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.