TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28254	84985;84986;84987	chr2:178561372;178561371;178561370	chr2:179426099;179426098;179426097
N2AB	26613	80062;80063;80064	chr2:178561372;178561371;178561370	chr2:179426099;179426098;179426097
N2A	25686	77281;77282;77283	chr2:178561372;178561371;178561370	chr2:179426099;179426098;179426097
N2B	19189	57790;57791;57792	chr2:178561372;178561371;178561370	chr2:179426099;179426098;179426097
Novex-1	19314	58165;58166;58167	chr2:178561372;178561371;178561370	chr2:179426099;179426098;179426097
Novex-2	19381	58366;58367;58368	chr2:178561372;178561371;178561370	chr2:179426099;179426098;179426097
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-94
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1801
• 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
D/N	None	None	0.684	N	0.542	0.332	0.247872288689	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.3796	ambiguous	0.3411	ambiguous	-0.559	Destabilizing	0.028	N	0.522	neutral	N	0.463567197	None	None	N
D/C	0.8367	likely_pathogenic	0.8251	pathogenic	-0.341	Destabilizing	0.996	D	0.804	deleterious	None	None	None	None	N
D/E	0.3738	ambiguous	0.3428	ambiguous	-0.763	Destabilizing	0.012	N	0.292	neutral	N	0.4681491	None	None	N
D/F	0.7703	likely_pathogenic	0.7593	pathogenic	-0.304	Destabilizing	0.953	D	0.821	deleterious	None	None	None	None	N
D/G	0.4334	ambiguous	0.4209	ambiguous	-0.916	Destabilizing	0.003	N	0.428	neutral	N	0.506392152	None	None	N
D/H	0.574	likely_pathogenic	0.5495	ambiguous	-0.807	Destabilizing	0.979	D	0.715	prob.delet.	D	0.525882133	None	None	N
D/I	0.7637	likely_pathogenic	0.7321	pathogenic	0.385	Stabilizing	0.953	D	0.805	deleterious	None	None	None	None	N
D/K	0.7835	likely_pathogenic	0.7588	pathogenic	-0.81	Destabilizing	0.742	D	0.608	neutral	None	None	None	None	N
D/L	0.6053	likely_pathogenic	0.5721	pathogenic	0.385	Stabilizing	0.742	D	0.765	deleterious	None	None	None	None	N
D/M	0.8244	likely_pathogenic	0.8043	pathogenic	0.853	Stabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
D/N	0.2682	likely_benign	0.2466	benign	-1.082	Destabilizing	0.684	D	0.542	neutral	N	0.497863149	None	None	N
D/P	0.9662	likely_pathogenic	0.9591	pathogenic	0.095	Stabilizing	0.953	D	0.693	prob.neutral	None	None	None	None	N
D/Q	0.642	likely_pathogenic	0.5971	pathogenic	-0.912	Destabilizing	0.742	D	0.571	neutral	None	None	None	None	N
D/R	0.8072	likely_pathogenic	0.775	pathogenic	-0.705	Destabilizing	0.91	D	0.747	deleterious	None	None	None	None	N
D/S	0.235	likely_benign	0.2022	benign	-1.375	Destabilizing	0.037	N	0.378	neutral	None	None	None	None	N
D/T	0.628	likely_pathogenic	0.5728	pathogenic	-1.093	Destabilizing	0.59	D	0.613	neutral	None	None	None	None	N
D/V	0.6113	likely_pathogenic	0.5621	ambiguous	0.095	Stabilizing	0.684	D	0.761	deleterious	N	0.515286296	None	None	N
D/W	0.9627	likely_pathogenic	0.96	pathogenic	-0.247	Destabilizing	0.996	D	0.811	deleterious	None	None	None	None	N
D/Y	0.4258	ambiguous	0.3945	ambiguous	-0.13	Destabilizing	0.979	D	0.819	deleterious	N	0.515032806	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.