TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18366	55321;55322;55323	chr2:178602306;178602305;178602304	chr2:179467033;179467032;179467031
N2AB	16725	50398;50399;50400	chr2:178602306;178602305;178602304	chr2:179467033;179467032;179467031
N2A	15798	47617;47618;47619	chr2:178602306;178602305;178602304	chr2:179467033;179467032;179467031
N2B	9301	28126;28127;28128	chr2:178602306;178602305;178602304	chr2:179467033;179467032;179467031
Novex-1	9426	28501;28502;28503	chr2:178602306;178602305;178602304	chr2:179467033;179467032;179467031
Novex-2	9493	28702;28703;28704	chr2:178602306;178602305;178602304	chr2:179467033;179467032;179467031
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: Fn3-21
• Domain position: 95
• Structural Position: 126
• Q(SASA): 0.4653
• 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/D	rs1269570668	-0.826	0.997	N	0.651	0.174	0.27855597813	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
E/D	rs1269570668	-0.826	0.997	N	0.651	0.174	0.27855597813	gnomAD-4.0.0	7.53128E-06	None	None	None	None	N	None	0	2.23974E-05	None	0	0	None	0	0	8.09886E-06	0	1.65804E-05
E/K	None	None	0.997	N	0.715	0.336	0.420570264827	gnomAD-4.0.0	1.59354E-06	None	None	None	None	N	None	0	0	None	0	2.78381E-05	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	0.1677	likely_benign	0.1976	benign	-0.776	Destabilizing	0.997	D	0.796	deleterious	N	0.450187444	None	None	N
E/C	0.7679	likely_pathogenic	0.8263	pathogenic	-0.395	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/D	0.1382	likely_benign	0.1534	benign	-0.808	Destabilizing	0.997	D	0.651	prob.neutral	N	0.485185452	None	None	N
E/F	0.6157	likely_pathogenic	0.6876	pathogenic	-0.372	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
E/G	0.2165	likely_benign	0.2738	benign	-1.065	Destabilizing	0.999	D	0.779	deleterious	N	0.512102695	None	None	N
E/H	0.5453	ambiguous	0.6243	pathogenic	-0.409	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
E/I	0.2803	likely_benign	0.3038	benign	-0.01	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
E/K	0.2753	likely_benign	0.3272	benign	-0.323	Destabilizing	0.997	D	0.715	prob.delet.	N	0.484492019	None	None	N
E/L	0.3802	ambiguous	0.4305	ambiguous	-0.01	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
E/M	0.4124	ambiguous	0.4543	ambiguous	0.253	Stabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
E/N	0.2659	likely_benign	0.2953	benign	-0.722	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
E/P	0.3735	ambiguous	0.4421	ambiguous	-0.245	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
E/Q	0.2059	likely_benign	0.2391	benign	-0.653	Destabilizing	0.999	D	0.632	neutral	N	0.497325244	None	None	N
E/R	0.4265	ambiguous	0.5057	ambiguous	-0.007	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
E/S	0.2231	likely_benign	0.2596	benign	-0.953	Destabilizing	0.998	D	0.689	prob.delet.	None	None	None	None	N
E/T	0.241	likely_benign	0.2685	benign	-0.721	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
E/V	0.1827	likely_benign	0.2037	benign	-0.245	Destabilizing	0.999	D	0.812	deleterious	N	0.481008997	None	None	N
E/W	0.8495	likely_pathogenic	0.8939	pathogenic	-0.121	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/Y	0.5493	ambiguous	0.6237	pathogenic	-0.124	Destabilizing	1.0	D	0.871	deleterious	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.