TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32247	96964;96965;96966	chr2:178543234;178543233;178543232	chr2:179407961;179407960;179407959
N2AB	30606	92041;92042;92043	chr2:178543234;178543233;178543232	chr2:179407961;179407960;179407959
N2A	29679	89260;89261;89262	chr2:178543234;178543233;178543232	chr2:179407961;179407960;179407959
N2B	23182	69769;69770;69771	chr2:178543234;178543233;178543232	chr2:179407961;179407960;179407959
Novex-1	23307	70144;70145;70146	chr2:178543234;178543233;178543232	chr2:179407961;179407960;179407959
Novex-2	23374	70345;70346;70347	chr2:178543234;178543233;178543232	chr2:179407961;179407960;179407959
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-123
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.5581
• 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	None	None	0.896	N	0.355	0.287	0.300449992093	gnomAD-4.0.0	3.18231E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86549E-05	0
E/Q	rs1695477466	None	0.946	N	0.319	0.243	0.328752806141	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/Q	rs1695477466	None	0.946	N	0.319	0.243	0.328752806141	gnomAD-4.0.0	6.57557E-06	None	None	None	None	N	None	0	6.5591E-05	None	0	0	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
E/A	0.1979	likely_benign	0.1825	benign	-0.084	Destabilizing	0.896	D	0.379	neutral	N	0.45156595	None	None	N
E/C	0.8794	likely_pathogenic	0.8571	pathogenic	-0.252	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
E/D	0.0922	likely_benign	0.0797	benign	-0.227	Destabilizing	0.004	N	0.213	neutral	N	0.369123499	None	None	N
E/F	0.8327	likely_pathogenic	0.7988	pathogenic	-0.115	Destabilizing	0.996	D	0.539	neutral	None	None	None	None	N
E/G	0.1515	likely_benign	0.14	benign	-0.198	Destabilizing	0.896	D	0.393	neutral	N	0.41791195	None	None	N
E/H	0.527	ambiguous	0.4978	ambiguous	0.511	Stabilizing	0.996	D	0.349	neutral	None	None	None	None	N
E/I	0.5676	likely_pathogenic	0.5087	ambiguous	0.159	Stabilizing	0.988	D	0.531	neutral	None	None	None	None	N
E/K	0.2252	likely_benign	0.2038	benign	0.31	Stabilizing	0.896	D	0.355	neutral	N	0.44502398	None	None	N
E/L	0.5126	ambiguous	0.47	ambiguous	0.159	Stabilizing	0.988	D	0.534	neutral	None	None	None	None	N
E/M	0.5909	likely_pathogenic	0.5529	ambiguous	-0.07	Destabilizing	0.999	D	0.521	neutral	None	None	None	None	N
E/N	0.2302	likely_benign	0.1968	benign	0.125	Stabilizing	0.851	D	0.332	neutral	None	None	None	None	N
E/P	0.4436	ambiguous	0.427	ambiguous	0.095	Stabilizing	0.988	D	0.388	neutral	None	None	None	None	N
E/Q	0.1795	likely_benign	0.1746	benign	0.137	Stabilizing	0.946	D	0.319	neutral	N	0.454200824	None	None	N
E/R	0.3505	ambiguous	0.3277	benign	0.572	Stabilizing	0.988	D	0.347	neutral	None	None	None	None	N
E/S	0.189	likely_benign	0.1711	benign	-0.045	Destabilizing	0.919	D	0.346	neutral	None	None	None	None	N
E/T	0.2539	likely_benign	0.2409	benign	0.055	Stabilizing	0.919	D	0.351	neutral	None	None	None	None	N
E/V	0.3356	likely_benign	0.3038	benign	0.095	Stabilizing	0.984	D	0.441	neutral	N	0.466284687	None	None	N
E/W	0.9145	likely_pathogenic	0.8956	pathogenic	-0.062	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/Y	0.708	likely_pathogenic	0.6608	pathogenic	0.105	Stabilizing	0.996	D	0.482	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.