TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22659	68200;68201;68202	chr2:178579055;178579054;178579053	chr2:179443782;179443781;179443780
N2AB	21018	63277;63278;63279	chr2:178579055;178579054;178579053	chr2:179443782;179443781;179443780
N2A	20091	60496;60497;60498	chr2:178579055;178579054;178579053	chr2:179443782;179443781;179443780
N2B	13594	41005;41006;41007	chr2:178579055;178579054;178579053	chr2:179443782;179443781;179443780
Novex-1	13719	41380;41381;41382	chr2:178579055;178579054;178579053	chr2:179443782;179443781;179443780
Novex-2	13786	41581;41582;41583	chr2:178579055;178579054;178579053	chr2:179443782;179443781;179443780
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-52
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.6552
• 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	rs1440927665	-0.26	None	N	0.097	0.122	0.0482279557977	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
E/D	rs1440927665	-0.26	None	N	0.097	0.122	0.0482279557977	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1440927665	-0.26	None	N	0.097	0.122	0.0482279557977	gnomAD-4.0.0	1.31527E-05	None	None	None	None	N	None	4.82556E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs778462661	None	0.324	N	0.448	0.257	0.215869574891	gnomAD-4.0.0	1.59244E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86012E-06	0	0
E/Q	None	None	0.324	N	0.444	0.207	0.152612264143	gnomAD-4.0.0	1.59244E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86012E-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
E/A	0.2698	likely_benign	0.2845	benign	-0.471	Destabilizing	0.324	N	0.429	neutral	N	0.468956845	None	None	N
E/C	0.9043	likely_pathogenic	0.9115	pathogenic	-0.019	Destabilizing	0.981	D	0.466	neutral	None	None	None	None	N
E/D	0.0735	likely_benign	0.078	benign	-0.703	Destabilizing	None	N	0.097	neutral	N	0.374390459	None	None	N
E/F	0.8526	likely_pathogenic	0.8622	pathogenic	-0.464	Destabilizing	0.932	D	0.409	neutral	None	None	None	None	N
E/G	0.2367	likely_benign	0.2463	benign	-0.736	Destabilizing	0.324	N	0.427	neutral	N	0.458643851	None	None	N
E/H	0.618	likely_pathogenic	0.6531	pathogenic	-0.714	Destabilizing	0.932	D	0.368	neutral	None	None	None	None	N
E/I	0.6391	likely_pathogenic	0.6568	pathogenic	0.213	Stabilizing	0.818	D	0.423	neutral	None	None	None	None	N
E/K	0.342	ambiguous	0.3906	ambiguous	-0.176	Destabilizing	0.324	N	0.448	neutral	N	0.48729189	None	None	N
E/L	0.5903	likely_pathogenic	0.6006	pathogenic	0.213	Stabilizing	0.818	D	0.418	neutral	None	None	None	None	N
E/M	0.6475	likely_pathogenic	0.6661	pathogenic	0.589	Stabilizing	0.981	D	0.361	neutral	None	None	None	None	N
E/N	0.2327	likely_benign	0.2543	benign	-0.349	Destabilizing	0.241	N	0.403	neutral	None	None	None	None	N
E/P	0.9134	likely_pathogenic	0.9173	pathogenic	0.007	Stabilizing	0.818	D	0.409	neutral	None	None	None	None	N
E/Q	0.265	likely_benign	0.287	benign	-0.301	Destabilizing	0.324	N	0.444	neutral	N	0.474074664	None	None	N
E/R	0.5055	ambiguous	0.5536	ambiguous	-0.069	Destabilizing	0.69	D	0.404	neutral	None	None	None	None	N
E/S	0.2298	likely_benign	0.2492	benign	-0.59	Destabilizing	0.116	N	0.412	neutral	None	None	None	None	N
E/T	0.2837	likely_benign	0.2906	benign	-0.39	Destabilizing	0.388	N	0.419	neutral	None	None	None	None	N
E/V	0.4145	ambiguous	0.435	ambiguous	0.007	Stabilizing	0.773	D	0.393	neutral	N	0.50980339	None	None	N
E/W	0.9441	likely_pathogenic	0.9516	pathogenic	-0.396	Destabilizing	0.981	D	0.564	neutral	None	None	None	None	N
E/Y	0.7268	likely_pathogenic	0.7469	pathogenic	-0.259	Destabilizing	0.932	D	0.389	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.