TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14519	43780;43781;43782	chr2:178632339;178632338;178632337	chr2:179497066;179497065;179497064
N2AB	12878	38857;38858;38859	chr2:178632339;178632338;178632337	chr2:179497066;179497065;179497064
N2A	11951	36076;36077;36078	chr2:178632339;178632338;178632337	chr2:179497066;179497065;179497064
N2B	5454	16585;16586;16587	chr2:178632339;178632338;178632337	chr2:179497066;179497065;179497064
Novex-1	5579	16960;16961;16962	chr2:178632339;178632338;178632337	chr2:179497066;179497065;179497064
Novex-2	5646	17161;17162;17163	chr2:178632339;178632338;178632337	chr2:179497066;179497065;179497064
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-96
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.3829
• 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/A	rs1284272355	-0.802	0.977	D	0.613	0.558	0.551798466036	gnomAD-2.1.1	4.25E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.46E-05	None	0	0	0
E/A	rs1284272355	-0.802	0.977	D	0.613	0.558	0.551798466036	gnomAD-4.0.0	1.61024E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46126E-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	0.2505	likely_benign	0.2352	benign	-1.132	Destabilizing	0.977	D	0.613	neutral	D	0.687967536	None	None	N
E/C	0.9279	likely_pathogenic	0.9268	pathogenic	-0.63	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/D	0.479	ambiguous	0.4712	ambiguous	-1.343	Destabilizing	0.977	D	0.393	neutral	D	0.688065158	None	None	N
E/F	0.8849	likely_pathogenic	0.889	pathogenic	-0.84	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
E/G	0.4462	ambiguous	0.4282	ambiguous	-1.497	Destabilizing	0.993	D	0.698	prob.neutral	D	0.690240522	None	None	N
E/H	0.7088	likely_pathogenic	0.6994	pathogenic	-1.08	Destabilizing	0.289	N	0.357	neutral	None	None	None	None	N
E/I	0.4985	ambiguous	0.4836	ambiguous	-0.124	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
E/K	0.2934	likely_benign	0.272	benign	-0.883	Destabilizing	0.977	D	0.486	neutral	D	0.605041652	None	None	N
E/L	0.6411	likely_pathogenic	0.6111	pathogenic	-0.124	Destabilizing	0.995	D	0.742	deleterious	None	None	None	None	N
E/M	0.5726	likely_pathogenic	0.5623	ambiguous	0.463	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/N	0.5773	likely_pathogenic	0.5504	ambiguous	-1.248	Destabilizing	0.995	D	0.631	neutral	None	None	None	None	N
E/P	0.9792	likely_pathogenic	0.9787	pathogenic	-0.441	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
E/Q	0.1906	likely_benign	0.1703	benign	-1.13	Destabilizing	0.993	D	0.583	neutral	D	0.646719307	None	None	N
E/R	0.4551	ambiguous	0.4414	ambiguous	-0.684	Destabilizing	0.995	D	0.643	neutral	None	None	None	None	N
E/S	0.3881	ambiguous	0.3586	ambiguous	-1.683	Destabilizing	0.983	D	0.53	neutral	None	None	None	None	N
E/T	0.3373	likely_benign	0.2892	benign	-1.369	Destabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	N
E/V	0.3081	likely_benign	0.2902	benign	-0.441	Destabilizing	0.997	D	0.745	deleterious	D	0.588195356	None	None	N
E/W	0.9724	likely_pathogenic	0.974	pathogenic	-0.68	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
E/Y	0.8506	likely_pathogenic	0.8538	pathogenic	-0.591	Destabilizing	0.99	D	0.747	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.