TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5651	17176;17177;17178	chr2:178731924;178731923;178731922	chr2:179596651;179596650;179596649
N2AB	5334	16225;16226;16227	chr2:178731924;178731923;178731922	chr2:179596651;179596650;179596649
N2A	4407	13444;13445;13446	chr2:178731924;178731923;178731922	chr2:179596651;179596650;179596649
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-40
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.8083
• 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/A	None	None	0.27	N	0.461	0.273	0.343788945184	gnomAD-4.0.0	1.59197E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4334E-05	0
E/G	rs1180270942	-0.304	0.001	N	0.242	0.236	0.149567049428	gnomAD-2.1.1	6.37E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.29601E-04	0
E/G	rs1180270942	-0.304	0.001	N	0.242	0.236	0.149567049428	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1180270942	-0.304	0.001	N	0.242	0.236	0.149567049428	gnomAD-4.0.0	2.56306E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.56917E-05	0	2.39388E-06	0	0
E/K	rs368458199	0.439	0.425	N	0.358	0.296	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs368458199	0.439	0.425	N	0.358	0.296	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs368458199	0.439	0.425	N	0.358	0.296	None	gnomAD-4.0.0	4.05986E-06	None	None	None	None	I	None	6.98714E-05	0	None	0	0	None	0	0	0	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	0.2091	likely_benign	0.1965	benign	-0.789	Destabilizing	0.27	N	0.461	neutral	N	0.46897078	None	None	I
E/C	0.9205	likely_pathogenic	0.8928	pathogenic	-0.464	Destabilizing	0.995	D	0.532	neutral	None	None	None	None	I
E/D	0.089	likely_benign	0.0825	benign	-0.668	Destabilizing	0.001	N	0.173	neutral	N	0.405804736	None	None	I
E/F	0.8694	likely_pathogenic	0.8379	pathogenic	-0.265	Destabilizing	0.981	D	0.545	neutral	None	None	None	None	I
E/G	0.1397	likely_benign	0.1236	benign	-1.072	Destabilizing	0.001	N	0.242	neutral	N	0.280202501	None	None	I
E/H	0.6886	likely_pathogenic	0.6434	pathogenic	-0.109	Destabilizing	0.944	D	0.407	neutral	None	None	None	None	I
E/I	0.6497	likely_pathogenic	0.6277	pathogenic	-0.039	Destabilizing	0.944	D	0.536	neutral	None	None	None	None	I
E/K	0.4212	ambiguous	0.3715	ambiguous	-0.232	Destabilizing	0.425	N	0.358	neutral	N	0.447691431	None	None	I
E/L	0.6512	likely_pathogenic	0.6157	pathogenic	-0.039	Destabilizing	0.828	D	0.541	neutral	None	None	None	None	I
E/M	0.6607	likely_pathogenic	0.6372	pathogenic	0.142	Stabilizing	0.995	D	0.525	neutral	None	None	None	None	I
E/N	0.2496	likely_benign	0.2178	benign	-0.773	Destabilizing	0.013	N	0.201	neutral	None	None	None	None	I
E/P	0.8047	likely_pathogenic	0.7687	pathogenic	-0.269	Destabilizing	0.828	D	0.501	neutral	None	None	None	None	I
E/Q	0.2594	likely_benign	0.2414	benign	-0.676	Destabilizing	0.784	D	0.39	neutral	N	0.45290525	None	None	I
E/R	0.5611	ambiguous	0.5031	ambiguous	0.167	Stabilizing	0.828	D	0.377	neutral	None	None	None	None	I
E/S	0.2337	likely_benign	0.2177	benign	-0.974	Destabilizing	0.495	N	0.38	neutral	None	None	None	None	I
E/T	0.3334	likely_benign	0.3202	benign	-0.736	Destabilizing	0.704	D	0.437	neutral	None	None	None	None	I
E/V	0.4332	ambiguous	0.4267	ambiguous	-0.269	Destabilizing	0.784	D	0.519	neutral	N	0.494002511	None	None	I
E/W	0.9492	likely_pathogenic	0.9307	pathogenic	0.032	Stabilizing	0.995	D	0.541	neutral	None	None	None	None	I
E/Y	0.7333	likely_pathogenic	0.6824	pathogenic	-0.008	Destabilizing	0.981	D	0.531	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.