TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7335	22228;22229;22230	chr2:178722896;178722895;178722894	chr2:179587623;179587622;179587621
N2AB	7018	21277;21278;21279	chr2:178722896;178722895;178722894	chr2:179587623;179587622;179587621
N2A	6091	18496;18497;18498	chr2:178722896;178722895;178722894	chr2:179587623;179587622;179587621
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-58
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.2054
• 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
A/T	rs1208605882	-0.982	None	N	0.187	0.124	0.0666544352282	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	9.19118E-04
A/T	rs1208605882	-0.982	None	N	0.187	0.124	0.0666544352282	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
A/T	rs1208605882	-0.982	None	N	0.187	0.124	0.0666544352282	gnomAD-4.0.0	4.0601E-06	None	None	None	None	N	None	0	6.15688E-05	None	0	0	None	0	0	3.615E-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
A/C	0.2534	likely_benign	0.2878	benign	-0.818	Destabilizing	0.64	D	0.502	neutral	None	None	None	None	N
A/D	0.1896	likely_benign	0.2381	benign	-0.585	Destabilizing	0.111	N	0.502	neutral	None	None	None	None	N
A/E	0.1938	likely_benign	0.2398	benign	-0.693	Destabilizing	0.052	N	0.487	neutral	N	0.452403817	None	None	N
A/F	0.1597	likely_benign	0.1949	benign	-0.965	Destabilizing	0.869	D	0.5	neutral	None	None	None	None	N
A/G	0.1037	likely_benign	0.1253	benign	-0.755	Destabilizing	0.004	N	0.353	neutral	N	0.520514321	None	None	N
A/H	0.283	likely_benign	0.3443	ambiguous	-0.777	Destabilizing	0.869	D	0.527	neutral	None	None	None	None	N
A/I	0.1195	likely_benign	0.1509	benign	-0.39	Destabilizing	0.162	N	0.508	neutral	None	None	None	None	N
A/K	0.262	likely_benign	0.3533	ambiguous	-0.899	Destabilizing	0.162	N	0.483	neutral	None	None	None	None	N
A/L	0.0988	likely_benign	0.1163	benign	-0.39	Destabilizing	0.078	N	0.446	neutral	None	None	None	None	N
A/M	0.1342	likely_benign	0.1596	benign	-0.381	Destabilizing	0.869	D	0.489	neutral	None	None	None	None	N
A/N	0.1425	likely_benign	0.1701	benign	-0.573	Destabilizing	0.014	N	0.49	neutral	None	None	None	None	N
A/P	0.1309	likely_benign	0.1786	benign	-0.424	Destabilizing	0.158	N	0.446	neutral	N	0.484228234	None	None	N
A/Q	0.2389	likely_benign	0.2927	benign	-0.812	Destabilizing	0.483	N	0.448	neutral	None	None	None	None	N
A/R	0.2412	likely_benign	0.3192	benign	-0.457	Destabilizing	0.483	N	0.465	neutral	None	None	None	None	N
A/S	0.0653	likely_benign	0.0665	benign	-0.87	Destabilizing	None	N	0.193	neutral	N	0.464407535	None	None	N
A/T	0.0653	likely_benign	0.0691	benign	-0.886	Destabilizing	None	N	0.187	neutral	N	0.439282591	None	None	N
A/V	0.086	likely_benign	0.0949	benign	-0.424	Destabilizing	None	N	0.189	neutral	N	0.47839834	None	None	N
A/W	0.3743	ambiguous	0.465	ambiguous	-1.163	Destabilizing	0.987	D	0.536	neutral	None	None	None	None	N
A/Y	0.2121	likely_benign	0.2706	benign	-0.796	Destabilizing	0.869	D	0.509	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.