TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7562	22909;22910;22911	chr2:178721979;178721978;178721977	chr2:179586706;179586705;179586704
N2AB	7245	21958;21959;21960	chr2:178721979;178721978;178721977	chr2:179586706;179586705;179586704
N2A	6318	19177;19178;19179	chr2:178721979;178721978;178721977	chr2:179586706;179586705;179586704
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-60
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.2944
• 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/I	rs1553909660	None	0.642	N	0.428	0.203	0.506373324096	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1553909660	None	0.642	N	0.428	0.203	0.506373324096	gnomAD-4.0.0	1.31439E-05	None	None	None	None	N	None	4.82486E-05	0	None	0	0	None	0	0	0	0	0
T/R	None	None	0.002	N	0.218	0.268	0.504297271243	gnomAD-4.0.0	1.5918E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-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
T/A	0.0844	likely_benign	0.0923	benign	-0.994	Destabilizing	0.002	N	0.124	neutral	N	0.519300813	None	None	N
T/C	0.5049	ambiguous	0.5312	ambiguous	-0.654	Destabilizing	0.944	D	0.431	neutral	None	None	None	None	N
T/D	0.4028	ambiguous	0.4929	ambiguous	-0.269	Destabilizing	0.329	N	0.399	neutral	None	None	None	None	N
T/E	0.3049	likely_benign	0.355	ambiguous	-0.175	Destabilizing	0.329	N	0.37	neutral	None	None	None	None	N
T/F	0.2536	likely_benign	0.287	benign	-0.822	Destabilizing	0.007	N	0.338	neutral	None	None	None	None	N
T/G	0.3399	likely_benign	0.3971	ambiguous	-1.335	Destabilizing	0.329	N	0.389	neutral	None	None	None	None	N
T/H	0.2035	likely_benign	0.2268	benign	-1.494	Destabilizing	0.944	D	0.507	neutral	None	None	None	None	N
T/I	0.1441	likely_benign	0.1726	benign	-0.146	Destabilizing	0.642	D	0.428	neutral	N	0.496637384	None	None	N
T/K	0.1859	likely_benign	0.1992	benign	-0.533	Destabilizing	0.001	N	0.171	neutral	N	0.434161986	None	None	N
T/L	0.0981	likely_benign	0.1088	benign	-0.146	Destabilizing	0.329	N	0.384	neutral	None	None	None	None	N
T/M	0.0861	likely_benign	0.0883	benign	-0.07	Destabilizing	0.981	D	0.44	neutral	None	None	None	None	N
T/N	0.1067	likely_benign	0.1286	benign	-0.76	Destabilizing	0.003	N	0.096	neutral	None	None	None	None	N
T/P	0.5886	likely_pathogenic	0.6836	pathogenic	-0.396	Destabilizing	0.784	D	0.48	neutral	N	0.487618567	None	None	N
T/Q	0.1817	likely_benign	0.1917	benign	-0.747	Destabilizing	0.704	D	0.433	neutral	None	None	None	None	N
T/R	0.1445	likely_benign	0.1627	benign	-0.533	Destabilizing	0.002	N	0.218	neutral	N	0.410151763	None	None	N
T/S	0.1044	likely_benign	0.1209	benign	-1.112	Destabilizing	0.139	N	0.281	neutral	N	0.456212127	None	None	N
T/V	0.1229	likely_benign	0.1418	benign	-0.396	Destabilizing	0.329	N	0.259	neutral	None	None	None	None	N
T/W	0.6199	likely_pathogenic	0.6483	pathogenic	-0.778	Destabilizing	0.995	D	0.499	neutral	None	None	None	None	N
T/Y	0.2753	likely_benign	0.2922	benign	-0.494	Destabilizing	0.543	D	0.529	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.