TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19972	60139;60140;60141	chr2:178591990;178591989;178591988	chr2:179456717;179456716;179456715
N2AB	18331	55216;55217;55218	chr2:178591990;178591989;178591988	chr2:179456717;179456716;179456715
N2A	17404	52435;52436;52437	chr2:178591990;178591989;178591988	chr2:179456717;179456716;179456715
N2B	10907	32944;32945;32946	chr2:178591990;178591989;178591988	chr2:179456717;179456716;179456715
Novex-1	11032	33319;33320;33321	chr2:178591990;178591989;178591988	chr2:179456717;179456716;179456715
Novex-2	11099	33520;33521;33522	chr2:178591990;178591989;178591988	chr2:179456717;179456716;179456715
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-32
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.2464
• 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
L/F	rs1553645773	None	0.026	N	0.339	0.035	0.265929055128	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
L/F	rs1553645773	None	0.026	N	0.339	0.035	0.265929055128	gnomAD-4.0.0	3.18893E-06	None	None	None	None	N	None	5.67859E-05	0	None	0	0	None	0	0	2.86138E-06	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
L/A	0.1401	likely_benign	0.1395	benign	-1.581	Destabilizing	0.007	N	0.389	neutral	None	None	None	None	N
L/C	0.3977	ambiguous	0.4176	ambiguous	-0.852	Destabilizing	0.492	N	0.295	neutral	None	None	None	None	N
L/D	0.6535	likely_pathogenic	0.6913	pathogenic	-1.353	Destabilizing	0.035	N	0.595	neutral	None	None	None	None	N
L/E	0.2903	likely_benign	0.2838	benign	-1.413	Destabilizing	0.018	N	0.519	neutral	None	None	None	None	N
L/F	0.1495	likely_benign	0.1656	benign	-1.375	Destabilizing	0.026	N	0.339	neutral	N	0.460681292	None	None	N
L/G	0.3966	ambiguous	0.4099	ambiguous	-1.834	Destabilizing	0.035	N	0.507	neutral	None	None	None	None	N
L/H	0.2356	likely_benign	0.2481	benign	-1.076	Destabilizing	0.204	N	0.499	neutral	None	None	None	None	N
L/I	0.0677	likely_benign	0.0703	benign	-0.983	Destabilizing	None	N	0.067	neutral	None	None	None	None	N
L/K	0.1836	likely_benign	0.178	benign	-1.067	Destabilizing	None	N	0.26	neutral	None	None	None	None	N
L/M	0.0753	likely_benign	0.075	benign	-0.594	Destabilizing	None	N	0.061	neutral	N	0.391168066	None	None	N
L/N	0.2931	likely_benign	0.3177	benign	-0.81	Destabilizing	0.112	N	0.634	neutral	None	None	None	None	N
L/P	0.8382	likely_pathogenic	0.8819	pathogenic	-1.151	Destabilizing	0.204	N	0.624	neutral	None	None	None	None	N
L/Q	0.1183	likely_benign	0.109	benign	-1.11	Destabilizing	0.001	N	0.325	neutral	None	None	None	None	N
L/R	0.1538	likely_benign	0.1474	benign	-0.345	Destabilizing	0.018	N	0.525	neutral	None	None	None	None	N
L/S	0.1675	likely_benign	0.1803	benign	-1.303	Destabilizing	0.026	N	0.419	neutral	N	0.423067053	None	None	N
L/T	0.1211	likely_benign	0.1219	benign	-1.263	Destabilizing	0.018	N	0.405	neutral	None	None	None	None	N
L/V	0.0647	likely_benign	0.0615	benign	-1.151	Destabilizing	None	N	0.052	neutral	N	0.389781199	None	None	N
L/W	0.3269	likely_benign	0.3632	ambiguous	-1.398	Destabilizing	0.69	D	0.501	neutral	N	0.461548084	None	None	N
L/Y	0.3634	ambiguous	0.3879	ambiguous	-1.191	Destabilizing	0.204	N	0.469	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.