TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6369	19330;19331;19332	chr2:178728933;178728932;178728931	chr2:179593660;179593659;179593658
N2AB	6052	18379;18380;18381	chr2:178728933;178728932;178728931	chr2:179593660;179593659;179593658
N2A	5125	15598;15599;15600	chr2:178728933;178728932;178728931	chr2:179593660;179593659;179593658
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-47
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.8031
• 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
E/G	None	None	0.994	N	0.401	0.568	0.499218193508	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs776552344	0.899	0.978	N	0.473	0.317	0.409937222855	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.32E-05	None	0	0	0
E/K	rs776552344	0.899	0.978	N	0.473	0.317	0.409937222855	gnomAD-4.0.0	6.85388E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16501E-05	0
E/Q	rs776552344	0.654	0.889	N	0.396	0.193	0.415055319159	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
E/Q	rs776552344	0.654	0.889	N	0.396	0.193	0.415055319159	gnomAD-4.0.0	3.42694E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.5024E-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
E/A	0.1634	likely_benign	0.1594	benign	0.003	Stabilizing	0.989	D	0.484	neutral	N	0.49829361	None	None	I
E/C	0.8977	likely_pathogenic	0.9121	pathogenic	0.003	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
E/D	0.096	likely_benign	0.1027	benign	-0.294	Destabilizing	0.217	N	0.418	neutral	N	0.432820766	None	None	I
E/F	0.7902	likely_pathogenic	0.8084	pathogenic	-0.111	Destabilizing	1.0	D	0.589	neutral	None	None	None	None	I
E/G	0.2226	likely_benign	0.2199	benign	-0.094	Destabilizing	0.994	D	0.401	neutral	N	0.511204192	None	None	I
E/H	0.5615	ambiguous	0.5875	pathogenic	0.378	Stabilizing	1.0	D	0.494	neutral	None	None	None	None	I
E/I	0.3492	ambiguous	0.3688	ambiguous	0.195	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	I
E/K	0.1912	likely_benign	0.2024	benign	0.527	Stabilizing	0.978	D	0.473	neutral	N	0.504430148	None	None	I
E/L	0.4832	ambiguous	0.5005	ambiguous	0.195	Stabilizing	0.999	D	0.56	neutral	None	None	None	None	I
E/M	0.5505	ambiguous	0.5652	pathogenic	0.096	Stabilizing	1.0	D	0.534	neutral	None	None	None	None	I
E/N	0.2738	likely_benign	0.3049	benign	0.33	Stabilizing	0.998	D	0.469	neutral	None	None	None	None	I
E/P	0.5256	ambiguous	0.4938	ambiguous	0.148	Stabilizing	1.0	D	0.479	neutral	None	None	None	None	I
E/Q	0.1972	likely_benign	0.2039	benign	0.333	Stabilizing	0.889	D	0.396	neutral	N	0.498640326	None	None	I
E/R	0.3419	ambiguous	0.352	ambiguous	0.634	Stabilizing	0.998	D	0.487	neutral	None	None	None	None	I
E/S	0.2172	likely_benign	0.2306	benign	0.209	Stabilizing	0.992	D	0.476	neutral	None	None	None	None	I
E/T	0.2659	likely_benign	0.2696	benign	0.298	Stabilizing	0.999	D	0.443	neutral	None	None	None	None	I
E/V	0.2344	likely_benign	0.2396	benign	0.148	Stabilizing	0.998	D	0.495	neutral	N	0.518458238	None	None	I
E/W	0.9246	likely_pathogenic	0.9331	pathogenic	-0.094	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
E/Y	0.6738	likely_pathogenic	0.6865	pathogenic	0.104	Stabilizing	1.0	D	0.533	neutral	None	None	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.