TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31950	96073;96074;96075	chr2:178544381;178544380;178544379	chr2:179409108;179409107;179409106
N2AB	30309	91150;91151;91152	chr2:178544381;178544380;178544379	chr2:179409108;179409107;179409106
N2A	29382	88369;88370;88371	chr2:178544381;178544380;178544379	chr2:179409108;179409107;179409106
N2B	22885	68878;68879;68880	chr2:178544381;178544380;178544379	chr2:179409108;179409107;179409106
Novex-1	23010	69253;69254;69255	chr2:178544381;178544380;178544379	chr2:179409108;179409107;179409106
Novex-2	23077	69454;69455;69456	chr2:178544381;178544380;178544379	chr2:179409108;179409107;179409106
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: Fn3-121
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2677
• 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/K	rs727505199	-0.651	0.999	N	0.559	0.401	0.344945010812	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs727505199	-0.651	0.999	N	0.559	0.401	0.344945010812	gnomAD-4.0.0	1.36847E-06	None	None	None	None	N	None	2.98793E-05	0	None	0	0	None	0	0	0	1.15934E-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	0.1512	likely_benign	0.1663	benign	-0.824	Destabilizing	0.999	D	0.64	neutral	N	0.476712324	None	None	N
E/C	0.781	likely_pathogenic	0.7996	pathogenic	-0.568	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
E/D	0.2278	likely_benign	0.2339	benign	-1.325	Destabilizing	0.999	D	0.428	neutral	N	0.433710908	None	None	N
E/F	0.7908	likely_pathogenic	0.7955	pathogenic	-0.204	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/G	0.1645	likely_benign	0.1697	benign	-1.233	Destabilizing	1.0	D	0.677	prob.neutral	N	0.464207174	None	None	N
E/H	0.5266	ambiguous	0.5413	ambiguous	-0.627	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/I	0.2956	likely_benign	0.3053	benign	0.306	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/K	0.1299	likely_benign	0.1334	benign	-1.069	Destabilizing	0.999	D	0.559	neutral	N	0.41597051	None	None	N
E/L	0.3027	likely_benign	0.3291	benign	0.306	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/M	0.3577	ambiguous	0.3811	ambiguous	0.822	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	N
E/N	0.3184	likely_benign	0.3364	benign	-1.491	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/P	0.3904	ambiguous	0.4317	ambiguous	-0.049	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Q	0.1282	likely_benign	0.1354	benign	-1.277	Destabilizing	1.0	D	0.61	neutral	N	0.482502146	None	None	N
E/R	0.2468	likely_benign	0.2527	benign	-0.786	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/S	0.2681	likely_benign	0.2897	benign	-1.858	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
E/T	0.2596	likely_benign	0.2811	benign	-1.522	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/V	0.1704	likely_benign	0.1804	benign	-0.049	Destabilizing	1.0	D	0.765	deleterious	N	0.450200513	None	None	N
E/W	0.9026	likely_pathogenic	0.9018	pathogenic	-0.045	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/Y	0.684	likely_pathogenic	0.6884	pathogenic	-0.006	Destabilizing	1.0	D	0.735	prob.delet.	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.