TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20008	60247;60248;60249	chr2:178591797;178591796;178591795	chr2:179456524;179456523;179456522
N2AB	18367	55324;55325;55326	chr2:178591797;178591796;178591795	chr2:179456524;179456523;179456522
N2A	17440	52543;52544;52545	chr2:178591797;178591796;178591795	chr2:179456524;179456523;179456522
N2B	10943	33052;33053;33054	chr2:178591797;178591796;178591795	chr2:179456524;179456523;179456522
Novex-1	11068	33427;33428;33429	chr2:178591797;178591796;178591795	chr2:179456524;179456523;179456522
Novex-2	11135	33628;33629;33630	chr2:178591797;178591796;178591795	chr2:179456524;179456523;179456522
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-33
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6909
• 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/L	rs199839492	-0.002	0.801	N	0.542	0.404	0.420447328233	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	1.68653E-04	None	0	None	0	0	0
P/L	rs199839492	-0.002	0.801	N	0.542	0.404	0.420447328233	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.94401E-04	None	0	0	0	0	0
P/L	rs199839492	-0.002	0.801	N	0.542	0.404	0.420447328233	gnomAD-4.0.0	5.57924E-06	None	None	None	None	I	None	0	0	None	0	2.01414E-04	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
P/A	0.0743	likely_benign	0.078	benign	-0.488	Destabilizing	0.625	D	0.439	neutral	N	0.478309834	None	None	I
P/C	0.4944	ambiguous	0.6078	pathogenic	-0.605	Destabilizing	0.998	D	0.509	neutral	None	None	None	None	I
P/D	0.34	likely_benign	0.3843	ambiguous	-0.176	Destabilizing	0.007	N	0.123	neutral	None	None	None	None	I
P/E	0.1985	likely_benign	0.2129	benign	-0.293	Destabilizing	0.002	N	0.159	neutral	None	None	None	None	I
P/F	0.5226	ambiguous	0.5847	pathogenic	-0.732	Destabilizing	0.991	D	0.518	neutral	None	None	None	None	I
P/G	0.3213	likely_benign	0.3676	ambiguous	-0.621	Destabilizing	0.688	D	0.478	neutral	None	None	None	None	I
P/H	0.1906	likely_benign	0.2098	benign	-0.205	Destabilizing	0.974	D	0.491	neutral	None	None	None	None	I
P/I	0.2585	likely_benign	0.2914	benign	-0.29	Destabilizing	0.974	D	0.539	neutral	None	None	None	None	I
P/K	0.1963	likely_benign	0.2075	benign	-0.349	Destabilizing	0.525	D	0.417	neutral	None	None	None	None	I
P/L	0.1304	likely_benign	0.145	benign	-0.29	Destabilizing	0.801	D	0.542	neutral	N	0.490174737	None	None	I
P/M	0.2893	likely_benign	0.3201	benign	-0.27	Destabilizing	0.998	D	0.471	neutral	None	None	None	None	I
P/N	0.2772	likely_benign	0.3109	benign	-0.083	Destabilizing	0.842	D	0.483	neutral	None	None	None	None	I
P/Q	0.1284	likely_benign	0.1391	benign	-0.341	Destabilizing	0.669	D	0.418	neutral	D	0.522023326	None	None	I
P/R	0.1597	likely_benign	0.1678	benign	0.162	Stabilizing	0.801	D	0.474	neutral	N	0.513923918	None	None	I
P/S	0.1336	likely_benign	0.1458	benign	-0.478	Destabilizing	0.625	D	0.415	neutral	N	0.502013413	None	None	I
P/T	0.1057	likely_benign	0.1135	benign	-0.492	Destabilizing	0.801	D	0.409	neutral	N	0.471777313	None	None	I
P/V	0.1624	likely_benign	0.1821	benign	-0.32	Destabilizing	0.915	D	0.488	neutral	None	None	None	None	I
P/W	0.674	likely_pathogenic	0.7355	pathogenic	-0.796	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	I
P/Y	0.4516	ambiguous	0.5088	ambiguous	-0.487	Destabilizing	0.991	D	0.524	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.