TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24629	74110;74111;74112	chr2:178572247;178572246;178572245	chr2:179436974;179436973;179436972
N2AB	22988	69187;69188;69189	chr2:178572247;178572246;178572245	chr2:179436974;179436973;179436972
N2A	22061	66406;66407;66408	chr2:178572247;178572246;178572245	chr2:179436974;179436973;179436972
N2B	15564	46915;46916;46917	chr2:178572247;178572246;178572245	chr2:179436974;179436973;179436972
Novex-1	15689	47290;47291;47292	chr2:178572247;178572246;178572245	chr2:179436974;179436973;179436972
Novex-2	15756	47491;47492;47493	chr2:178572247;178572246;178572245	chr2:179436974;179436973;179436972
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-67
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.1488
• 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
T/A	rs1708480217	None	0.039	N	0.197	0.253	0.192905019026	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06697E-04	0
T/A	rs1708480217	None	0.039	N	0.197	0.253	0.192905019026	gnomAD-4.0.0	4.9589E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.78542E-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
T/A	0.5572	ambiguous	0.519	ambiguous	-0.629	Destabilizing	0.039	N	0.197	neutral	N	0.485161534	None	None	N
T/C	0.8817	likely_pathogenic	0.873	pathogenic	-0.773	Destabilizing	1.0	D	0.505	neutral	None	None	None	None	N
T/D	0.8269	likely_pathogenic	0.8139	pathogenic	-1.624	Destabilizing	0.978	D	0.471	neutral	None	None	None	None	N
T/E	0.9054	likely_pathogenic	0.8928	pathogenic	-1.604	Destabilizing	0.993	D	0.464	neutral	None	None	None	None	N
T/F	0.9171	likely_pathogenic	0.8866	pathogenic	-0.906	Destabilizing	1.0	D	0.588	neutral	None	None	None	None	N
T/G	0.4828	ambiguous	0.458	ambiguous	-0.865	Destabilizing	0.991	D	0.467	neutral	None	None	None	None	N
T/H	0.7407	likely_pathogenic	0.7108	pathogenic	-1.258	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	N
T/I	0.9624	likely_pathogenic	0.95	pathogenic	-0.089	Destabilizing	0.997	D	0.516	neutral	N	0.5038749	None	None	N
T/K	0.7489	likely_pathogenic	0.7335	pathogenic	-0.804	Destabilizing	0.994	D	0.473	neutral	N	0.488528896	None	None	N
T/L	0.6567	likely_pathogenic	0.5961	pathogenic	-0.089	Destabilizing	0.983	D	0.443	neutral	None	None	None	None	N
T/M	0.4778	ambiguous	0.4099	ambiguous	0.264	Stabilizing	1.0	D	0.507	neutral	None	None	None	None	N
T/N	0.3996	ambiguous	0.3948	ambiguous	-1.097	Destabilizing	0.978	D	0.501	neutral	None	None	None	None	N
T/P	0.9235	likely_pathogenic	0.9173	pathogenic	-0.239	Destabilizing	0.985	D	0.522	neutral	N	0.521979155	None	None	N
T/Q	0.7019	likely_pathogenic	0.6823	pathogenic	-1.368	Destabilizing	0.995	D	0.519	neutral	None	None	None	None	N
T/R	0.7271	likely_pathogenic	0.7094	pathogenic	-0.494	Destabilizing	0.999	D	0.525	neutral	N	0.47699478	None	None	N
T/S	0.2005	likely_benign	0.1838	benign	-1.133	Destabilizing	0.106	N	0.273	neutral	N	0.491815062	None	None	N
T/V	0.8922	likely_pathogenic	0.8718	pathogenic	-0.239	Destabilizing	0.976	D	0.435	neutral	None	None	None	None	N
T/W	0.9775	likely_pathogenic	0.9666	pathogenic	-0.957	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
T/Y	0.9028	likely_pathogenic	0.8779	pathogenic	-0.603	Destabilizing	1.0	D	0.585	neutral	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.