TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7096	21511;21512;21513	chr2:178723973;178723972;178723971	chr2:179588700;179588699;179588698
N2AB	6779	20560;20561;20562	chr2:178723973;178723972;178723971	chr2:179588700;179588699;179588698
N2A	5852	17779;17780;17781	chr2:178723973;178723972;178723971	chr2:179588700;179588699;179588698
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-55
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.8227
• 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/E	rs1482277729	-0.1	0.006	N	0.119	0.049	0.0762999501168	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/E	rs1482277729	-0.1	0.006	N	0.119	0.049	0.0762999501168	gnomAD-4.0.0	6.84317E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15947E-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
D/A	0.243	likely_benign	0.302	benign	0.009	Stabilizing	0.505	D	0.425	neutral	N	0.459833171	None	None	N
D/C	0.7229	likely_pathogenic	0.7915	pathogenic	-0.125	Destabilizing	0.991	D	0.541	neutral	None	None	None	None	N
D/E	0.1831	likely_benign	0.2017	benign	-0.284	Destabilizing	0.006	N	0.119	neutral	N	0.440855019	None	None	N
D/F	0.743	likely_pathogenic	0.8055	pathogenic	-0.013	Destabilizing	0.967	D	0.473	neutral	None	None	None	None	N
D/G	0.1416	likely_benign	0.176	benign	-0.114	Destabilizing	0.338	N	0.398	neutral	N	0.473751298	None	None	N
D/H	0.3428	ambiguous	0.3953	ambiguous	0.568	Stabilizing	0.782	D	0.377	neutral	N	0.471291608	None	None	N
D/I	0.6303	likely_pathogenic	0.7369	pathogenic	0.27	Stabilizing	0.906	D	0.472	neutral	None	None	None	None	N
D/K	0.4065	ambiguous	0.4831	ambiguous	0.487	Stabilizing	0.404	N	0.396	neutral	None	None	None	None	N
D/L	0.5508	ambiguous	0.6451	pathogenic	0.27	Stabilizing	0.826	D	0.47	neutral	None	None	None	None	N
D/M	0.7609	likely_pathogenic	0.8223	pathogenic	0.084	Stabilizing	0.991	D	0.48	neutral	None	None	None	None	N
D/N	0.1056	likely_benign	0.117	benign	0.155	Stabilizing	0.001	N	0.119	neutral	N	0.489686329	None	None	N
D/P	0.7545	likely_pathogenic	0.8372	pathogenic	0.203	Stabilizing	0.906	D	0.391	neutral	None	None	None	None	N
D/Q	0.3737	ambiguous	0.4363	ambiguous	0.175	Stabilizing	0.826	D	0.332	neutral	None	None	None	None	N
D/R	0.4275	ambiguous	0.5063	ambiguous	0.716	Stabilizing	0.826	D	0.425	neutral	None	None	None	None	N
D/S	0.145	likely_benign	0.1672	benign	0.083	Stabilizing	0.404	N	0.358	neutral	None	None	None	None	N
D/T	0.3787	ambiguous	0.4557	ambiguous	0.191	Stabilizing	0.404	N	0.427	neutral	None	None	None	None	N
D/V	0.3946	ambiguous	0.5142	ambiguous	0.203	Stabilizing	0.879	D	0.471	neutral	N	0.479040289	None	None	N
D/W	0.8957	likely_pathogenic	0.9258	pathogenic	0.049	Stabilizing	0.991	D	0.611	neutral	None	None	None	None	N
D/Y	0.3336	likely_benign	0.3921	ambiguous	0.218	Stabilizing	0.957	D	0.471	neutral	N	0.503892494	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.