TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3993	12202;12203;12204	chr2:178741256;178741255;178741254	chr2:179605983;179605982;179605981
N2AB	3676	11251;11252;11253	chr2:178741256;178741255;178741254	chr2:179605983;179605982;179605981
N2A	None	None	chr2:None	chr2:None
N2B	3630	11113;11114;11115	chr2:178741256;178741255;178741254	chr2:179605983;179605982;179605981
Novex-1	3755	11488;11489;11490	chr2:178741256;178741255;178741254	chr2:179605983;179605982;179605981
Novex-2	3822	11689;11690;11691	chr2:178741256;178741255;178741254	chr2:179605983;179605982;179605981
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-28
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.2999
• 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
S/P	rs771077873	0.335	0.896	D	0.525	0.253	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
S/P	rs771077873	0.335	0.896	D	0.525	0.253	None	gnomAD-4.0.0	3.18292E-06	None	None	None	None	I	None	0	2.28655E-05	None	0	0	None	0	0	0	0	3.02425E-05

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
S/A	0.0883	likely_benign	0.0885	benign	-0.543	Destabilizing	0.004	N	0.157	neutral	N	0.499148553	None	None	I
S/C	0.1102	likely_benign	0.1109	benign	-0.535	Destabilizing	0.97	D	0.501	neutral	D	0.557523696	None	None	I
S/D	0.2918	likely_benign	0.2802	benign	-1.204	Destabilizing	0.447	N	0.413	neutral	None	None	None	None	I
S/E	0.3557	ambiguous	0.3544	ambiguous	-1.193	Destabilizing	0.005	N	0.277	neutral	None	None	None	None	I
S/F	0.1548	likely_benign	0.1462	benign	-0.853	Destabilizing	0.81	D	0.604	neutral	D	0.567472252	None	None	I
S/G	0.1279	likely_benign	0.1213	benign	-0.786	Destabilizing	0.447	N	0.413	neutral	None	None	None	None	I
S/H	0.2983	likely_benign	0.2918	benign	-1.389	Destabilizing	0.977	D	0.505	neutral	None	None	None	None	I
S/I	0.1666	likely_benign	0.1596	benign	-0.004	Destabilizing	0.447	N	0.587	neutral	None	None	None	None	I
S/K	0.5142	ambiguous	0.4997	ambiguous	-0.737	Destabilizing	0.447	N	0.413	neutral	None	None	None	None	I
S/L	0.1021	likely_benign	0.1008	benign	-0.004	Destabilizing	0.005	N	0.417	neutral	None	None	None	None	I
S/M	0.223	likely_benign	0.2166	benign	0.392	Stabilizing	0.85	D	0.517	neutral	None	None	None	None	I
S/N	0.141	likely_benign	0.1408	benign	-0.923	Destabilizing	0.617	D	0.469	neutral	None	None	None	None	I
S/P	0.7145	likely_pathogenic	0.6812	pathogenic	-0.15	Destabilizing	0.896	D	0.525	neutral	D	0.54944927	None	None	I
S/Q	0.4309	ambiguous	0.4314	ambiguous	-1.13	Destabilizing	0.739	D	0.475	neutral	None	None	None	None	I
S/R	0.3952	ambiguous	0.3908	ambiguous	-0.59	Destabilizing	0.85	D	0.526	neutral	None	None	None	None	I
S/T	0.0907	likely_benign	0.0886	benign	-0.767	Destabilizing	0.004	N	0.279	neutral	N	0.490463026	None	None	I
S/V	0.2038	likely_benign	0.1911	benign	-0.15	Destabilizing	0.447	N	0.559	neutral	None	None	None	None	I
S/W	0.2805	likely_benign	0.2585	benign	-0.933	Destabilizing	0.992	D	0.659	neutral	None	None	None	None	I
S/Y	0.1532	likely_benign	0.144	benign	-0.596	Destabilizing	0.896	D	0.598	neutral	N	0.512309973	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.