TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25271	76036;76037;76038	chr2:178570321;178570320;178570319	chr2:179435048;179435047;179435046
N2AB	23630	71113;71114;71115	chr2:178570321;178570320;178570319	chr2:179435048;179435047;179435046
N2A	22703	68332;68333;68334	chr2:178570321;178570320;178570319	chr2:179435048;179435047;179435046
N2B	16206	48841;48842;48843	chr2:178570321;178570320;178570319	chr2:179435048;179435047;179435046
Novex-1	16331	49216;49217;49218	chr2:178570321;178570320;178570319	chr2:179435048;179435047;179435046
Novex-2	16398	49417;49418;49419	chr2:178570321;178570320;178570319	chr2:179435048;179435047;179435046
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: Fn3-71
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.5569
• 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/G	rs1163400034	-0.789	0.324	N	0.453	0.325	0.372087925617	gnomAD-2.1.1	7.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
E/G	rs1163400034	-0.789	0.324	N	0.453	0.325	0.372087925617	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1163400034	-0.789	0.324	N	0.453	0.325	0.372087925617	gnomAD-4.0.0	1.02553E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.91524E-05	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	0.1133	likely_benign	0.1299	benign	-0.456	Destabilizing	0.09	N	0.398	neutral	N	0.474920026	None	None	N
E/C	0.8204	likely_pathogenic	0.8634	pathogenic	0.092	Stabilizing	0.981	D	0.533	neutral	None	None	None	None	N
E/D	0.258	likely_benign	0.3099	benign	-0.459	Destabilizing	0.165	N	0.464	neutral	N	0.470180697	None	None	N
E/F	0.8398	likely_pathogenic	0.8755	pathogenic	-0.505	Destabilizing	0.932	D	0.485	neutral	None	None	None	None	N
E/G	0.2438	likely_benign	0.2581	benign	-0.676	Destabilizing	0.324	N	0.453	neutral	N	0.491830124	None	None	N
E/H	0.5264	ambiguous	0.5933	pathogenic	-0.574	Destabilizing	0.818	D	0.386	neutral	None	None	None	None	N
E/I	0.3724	ambiguous	0.4377	ambiguous	0.096	Stabilizing	0.818	D	0.492	neutral	None	None	None	None	N
E/K	0.1683	likely_benign	0.1842	benign	0.14	Stabilizing	0.001	N	0.19	neutral	N	0.447293494	None	None	N
E/L	0.4163	ambiguous	0.4774	ambiguous	0.096	Stabilizing	0.388	N	0.501	neutral	None	None	None	None	N
E/M	0.4742	ambiguous	0.542	ambiguous	0.418	Stabilizing	0.981	D	0.443	neutral	None	None	None	None	N
E/N	0.4278	ambiguous	0.4877	ambiguous	-0.049	Destabilizing	0.69	D	0.418	neutral	None	None	None	None	N
E/P	0.2732	likely_benign	0.3066	benign	-0.067	Destabilizing	0.001	N	0.171	neutral	None	None	None	None	N
E/Q	0.1286	likely_benign	0.1421	benign	-0.025	Destabilizing	0.193	N	0.506	neutral	N	0.480597991	None	None	N
E/R	0.2655	likely_benign	0.2957	benign	0.229	Stabilizing	0.241	N	0.45	neutral	None	None	None	None	N
E/S	0.2347	likely_benign	0.2754	benign	-0.252	Destabilizing	0.241	N	0.417	neutral	None	None	None	None	N
E/T	0.252	likely_benign	0.2944	benign	-0.082	Destabilizing	0.388	N	0.466	neutral	None	None	None	None	N
E/V	0.2027	likely_benign	0.2368	benign	-0.067	Destabilizing	0.324	N	0.467	neutral	N	0.46869944	None	None	N
E/W	0.9393	likely_pathogenic	0.9574	pathogenic	-0.415	Destabilizing	0.981	D	0.581	neutral	None	None	None	None	N
E/Y	0.724	likely_pathogenic	0.7777	pathogenic	-0.283	Destabilizing	0.932	D	0.465	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.