TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5401	16426;16427;16428	chr2:178732975;178732974;178732973	chr2:179597702;179597701;179597700
N2AB	5084	15475;15476;15477	chr2:178732975;178732974;178732973	chr2:179597702;179597701;179597700
N2A	4157	12694;12695;12696	chr2:178732975;178732974;178732973	chr2:179597702;179597701;179597700
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: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-37
• Domain position: 45
• Structural Position: 111
• Q(SASA): 0.9514
• Predicted PPI site: I

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	rs1349486698	None	0.183	N	0.218	0.083	0.19670166235	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/E	rs1349486698	None	0.183	N	0.218	0.083	0.19670166235	gnomAD-4.0.0	6.84299E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15945E-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	0.1117	likely_benign	0.1153	benign	0.07	Stabilizing	0.001	N	0.142	neutral	N	0.419999745	None	None	I
D/C	0.4787	ambiguous	0.4774	ambiguous	-0.054	Destabilizing	0.983	D	0.198	neutral	None	None	None	None	I
D/E	0.0982	likely_benign	0.1044	benign	-0.263	Destabilizing	0.183	N	0.218	neutral	N	0.41797816	None	None	I
D/F	0.4612	ambiguous	0.4596	ambiguous	-0.007	Destabilizing	0.716	D	0.223	neutral	None	None	None	None	I
D/G	0.1008	likely_benign	0.1006	benign	-0.043	Destabilizing	0.101	N	0.294	neutral	N	0.384422946	None	None	I
D/H	0.1738	likely_benign	0.1688	benign	0.539	Stabilizing	0.655	D	0.222	neutral	N	0.447533062	None	None	I
D/I	0.2842	likely_benign	0.2853	benign	0.299	Stabilizing	0.264	N	0.303	neutral	None	None	None	None	I
D/K	0.1976	likely_benign	0.195	benign	0.527	Stabilizing	0.264	N	0.266	neutral	None	None	None	None	I
D/L	0.2563	likely_benign	0.2562	benign	0.299	Stabilizing	0.002	N	0.259	neutral	None	None	None	None	I
D/M	0.4676	ambiguous	0.4786	ambiguous	0.126	Stabilizing	0.716	D	0.209	neutral	None	None	None	None	I
D/N	0.0817	likely_benign	0.0831	benign	0.252	Stabilizing	0.002	N	0.169	neutral	N	0.419191668	None	None	I
D/P	0.2496	likely_benign	0.2582	benign	0.242	Stabilizing	0.002	N	0.225	neutral	None	None	None	None	I
D/Q	0.1859	likely_benign	0.1886	benign	0.266	Stabilizing	0.418	N	0.233	neutral	None	None	None	None	I
D/R	0.215	likely_benign	0.2095	benign	0.707	Stabilizing	0.418	N	0.273	neutral	None	None	None	None	I
D/S	0.0833	likely_benign	0.0848	benign	0.177	Stabilizing	0.027	N	0.163	neutral	None	None	None	None	I
D/T	0.1699	likely_benign	0.1735	benign	0.276	Stabilizing	0.004	N	0.149	neutral	None	None	None	None	I
D/V	0.1768	likely_benign	0.1774	benign	0.242	Stabilizing	0.101	N	0.24	neutral	N	0.479664124	None	None	I
D/W	0.732	likely_pathogenic	0.7325	pathogenic	0.03	Stabilizing	0.983	D	0.217	neutral	None	None	None	None	I
D/Y	0.1982	likely_benign	0.1921	benign	0.219	Stabilizing	0.921	D	0.221	neutral	N	0.45749934	None	None	I

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.