TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26021	78286;78287;78288	chr2:178568071;178568070;178568069	chr2:179432798;179432797;179432796
N2AB	24380	73363;73364;73365	chr2:178568071;178568070;178568069	chr2:179432798;179432797;179432796
N2A	23453	70582;70583;70584	chr2:178568071;178568070;178568069	chr2:179432798;179432797;179432796
N2B	16956	51091;51092;51093	chr2:178568071;178568070;178568069	chr2:179432798;179432797;179432796
Novex-1	17081	51466;51467;51468	chr2:178568071;178568070;178568069	chr2:179432798;179432797;179432796
Novex-2	17148	51667;51668;51669	chr2:178568071;178568070;178568069	chr2:179432798;179432797;179432796
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-77
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7098
• Predicted PPI site: I

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
P/R	rs727504982	0.222	0.001	N	0.13	0.24	0.252162846088	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	9.19118E-04
P/R	rs727504982	0.222	0.001	N	0.13	0.24	0.252162846088	gnomAD-4.0.0	7.96077E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.76605E-05	0	8.57898E-06	0	0
P/T	None	None	0.166	N	0.409	0.274	0.292062946507	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.0583	likely_benign	0.056	benign	-0.555	Destabilizing	0.002	N	0.099	neutral	N	0.50039726	None	None	I
P/C	0.3594	ambiguous	0.3289	benign	-0.664	Destabilizing	0.965	D	0.533	neutral	None	None	None	None	I
P/D	0.2891	likely_benign	0.2628	benign	-0.264	Destabilizing	0.209	N	0.394	neutral	None	None	None	None	I
P/E	0.1734	likely_benign	0.1629	benign	-0.373	Destabilizing	0.209	N	0.4	neutral	None	None	None	None	I
P/F	0.4478	ambiguous	0.4192	ambiguous	-0.734	Destabilizing	0.818	D	0.549	neutral	None	None	None	None	I
P/G	0.2846	likely_benign	0.2519	benign	-0.7	Destabilizing	0.103	N	0.401	neutral	None	None	None	None	I
P/H	0.1438	likely_benign	0.1325	benign	-0.249	Destabilizing	0.873	D	0.511	neutral	N	0.491553862	None	None	I
P/I	0.2189	likely_benign	0.1974	benign	-0.321	Destabilizing	0.39	N	0.555	neutral	None	None	None	None	I
P/K	0.1448	likely_benign	0.1329	benign	-0.469	Destabilizing	0.002	N	0.085	neutral	None	None	None	None	I
P/L	0.1018	likely_benign	0.0958	benign	-0.321	Destabilizing	0.001	N	0.126	neutral	N	0.489187232	None	None	I
P/M	0.2004	likely_benign	0.1887	benign	-0.34	Destabilizing	0.818	D	0.513	neutral	None	None	None	None	I
P/N	0.198	likely_benign	0.1649	benign	-0.215	Destabilizing	0.007	N	0.116	neutral	None	None	None	None	I
P/Q	0.0975	likely_benign	0.089	benign	-0.458	Destabilizing	0.561	D	0.463	neutral	None	None	None	None	I
P/R	0.1221	likely_benign	0.1192	benign	0.057	Stabilizing	0.001	N	0.13	neutral	N	0.50395764	None	None	I
P/S	0.1058	likely_benign	0.0906	benign	-0.607	Destabilizing	0.016	N	0.081	neutral	N	0.511440973	None	None	I
P/T	0.0799	likely_benign	0.0712	benign	-0.611	Destabilizing	0.166	N	0.409	neutral	N	0.486096133	None	None	I
P/V	0.1403	likely_benign	0.1308	benign	-0.364	Destabilizing	0.209	N	0.42	neutral	None	None	None	None	I
P/W	0.6031	likely_pathogenic	0.6052	pathogenic	-0.803	Destabilizing	0.991	D	0.525	neutral	None	None	None	None	I
P/Y	0.3832	ambiguous	0.3656	ambiguous	-0.508	Destabilizing	0.901	D	0.55	neutral	None	None	None	None	I

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.