TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32708	98347;98348;98349	chr2:178539943;178539942;178539941	chr2:179404670;179404669;179404668
N2AB	31067	93424;93425;93426	chr2:178539943;178539942;178539941	chr2:179404670;179404669;179404668
N2A	30140	90643;90644;90645	chr2:178539943;178539942;178539941	chr2:179404670;179404669;179404668
N2B	23643	71152;71153;71154	chr2:178539943;178539942;178539941	chr2:179404670;179404669;179404668
Novex-1	23768	71527;71528;71529	chr2:178539943;178539942;178539941	chr2:179404670;179404669;179404668
Novex-2	23835	71728;71729;71730	chr2:178539943;178539942;178539941	chr2:179404670;179404669;179404668
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: Ig-155
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5745
• 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/K	rs1428233034	0.255	0.064	N	0.171	0.227	0.268211541103	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	8.7E-05	None	0	0	None	0	None	0	0	1.66168E-04
E/K	rs1428233034	0.255	0.064	N	0.171	0.227	0.268211541103	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs1428233034	0.255	0.064	N	0.171	0.227	0.268211541103	gnomAD-4.0.0	4.33876E-06	None	None	None	None	N	None	0	1.00043E-04	None	0	0	None	0	0	8.47745E-07	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	0.1287	likely_benign	0.1422	benign	-0.011	Destabilizing	0.028	N	0.17	neutral	N	0.425982433	None	None	N
E/C	0.7213	likely_pathogenic	0.747	pathogenic	-0.261	Destabilizing	0.998	D	0.351	neutral	None	None	None	None	N
E/D	0.1046	likely_benign	0.1149	benign	-0.261	Destabilizing	0.679	D	0.263	neutral	N	0.4273693	None	None	N
E/F	0.6439	likely_pathogenic	0.6824	pathogenic	-0.068	Destabilizing	0.98	D	0.384	neutral	None	None	None	None	N
E/G	0.1186	likely_benign	0.1403	benign	-0.122	Destabilizing	0.007	N	0.191	neutral	N	0.427889375	None	None	N
E/H	0.3557	ambiguous	0.4001	ambiguous	0.584	Stabilizing	0.047	N	0.181	neutral	None	None	None	None	N
E/I	0.2933	likely_benign	0.3163	benign	0.222	Stabilizing	0.98	D	0.413	neutral	None	None	None	None	N
E/K	0.1035	likely_benign	0.1267	benign	0.35	Stabilizing	0.064	N	0.171	neutral	N	0.425982433	None	None	N
E/L	0.3251	likely_benign	0.35	ambiguous	0.222	Stabilizing	0.872	D	0.393	neutral	None	None	None	None	N
E/M	0.401	ambiguous	0.4195	ambiguous	-0.063	Destabilizing	0.993	D	0.342	neutral	None	None	None	None	N
E/N	0.2008	likely_benign	0.2319	benign	0.174	Stabilizing	0.872	D	0.221	neutral	None	None	None	None	N
E/P	0.2566	likely_benign	0.2943	benign	0.161	Stabilizing	0.932	D	0.389	neutral	None	None	None	None	N
E/Q	0.1258	likely_benign	0.1422	benign	0.17	Stabilizing	0.837	D	0.251	neutral	N	0.426675867	None	None	N
E/R	0.1823	likely_benign	0.2164	benign	0.62	Stabilizing	0.021	N	0.183	neutral	None	None	None	None	N
E/S	0.1404	likely_benign	0.1602	benign	None	Stabilizing	0.209	N	0.165	neutral	None	None	None	None	N
E/T	0.1784	likely_benign	0.1982	benign	0.096	Stabilizing	0.773	D	0.355	neutral	None	None	None	None	N
E/V	0.1915	likely_benign	0.2082	benign	0.161	Stabilizing	0.837	D	0.365	neutral	N	0.428062733	None	None	N
E/W	0.7976	likely_pathogenic	0.8239	pathogenic	-0.029	Destabilizing	0.998	D	0.351	neutral	None	None	None	None	N
E/Y	0.5042	ambiguous	0.5396	ambiguous	0.154	Stabilizing	0.96	D	0.391	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.