TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25592	76999;77000;77001	chr2:178569358;178569357;178569356	chr2:179434085;179434084;179434083
N2AB	23951	72076;72077;72078	chr2:178569358;178569357;178569356	chr2:179434085;179434084;179434083
N2A	23024	69295;69296;69297	chr2:178569358;178569357;178569356	chr2:179434085;179434084;179434083
N2B	16527	49804;49805;49806	chr2:178569358;178569357;178569356	chr2:179434085;179434084;179434083
Novex-1	16652	50179;50180;50181	chr2:178569358;178569357;178569356	chr2:179434085;179434084;179434083
Novex-2	16719	50380;50381;50382	chr2:178569358;178569357;178569356	chr2:179434085;179434084;179434083
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-135
• Domain position: 79
• Structural Position: 169
• Q(SASA): 0.2664
• 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	None	None	0.008	D	0.409	0.235	0.31411915649	gnomAD-4.0.0	3.18432E-06	None	None	None	None	N	None	0	0	None	0	5.54816E-05	None	0	0	0	0	0
A/V	rs1707265300	None	0.075	N	0.389	0.262	0.398283496042	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43382E-05	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	0.5011	ambiguous	0.5801	pathogenic	-0.776	Destabilizing	0.996	D	0.64	neutral	None	None	None	None	N
A/D	0.8587	likely_pathogenic	0.8787	pathogenic	-0.05	Destabilizing	0.901	D	0.739	prob.delet.	N	0.51567723	None	None	N
A/E	0.8222	likely_pathogenic	0.8432	pathogenic	-0.147	Destabilizing	0.923	D	0.703	prob.neutral	None	None	None	None	N
A/F	0.5879	likely_pathogenic	0.6561	pathogenic	-0.663	Destabilizing	0.961	D	0.777	deleterious	None	None	None	None	N
A/G	0.2731	likely_benign	0.3101	benign	-0.447	Destabilizing	0.565	D	0.577	neutral	N	0.494383425	None	None	N
A/H	0.8674	likely_pathogenic	0.889	pathogenic	-0.463	Destabilizing	0.996	D	0.757	deleterious	None	None	None	None	N
A/I	0.3071	likely_benign	0.4008	ambiguous	-0.134	Destabilizing	0.633	D	0.686	prob.neutral	None	None	None	None	N
A/K	0.9282	likely_pathogenic	0.9476	pathogenic	-0.601	Destabilizing	0.923	D	0.709	prob.delet.	None	None	None	None	N
A/L	0.3251	likely_benign	0.394	ambiguous	-0.134	Destabilizing	0.633	D	0.599	neutral	None	None	None	None	N
A/M	0.3601	ambiguous	0.4375	ambiguous	-0.357	Destabilizing	0.989	D	0.717	prob.delet.	None	None	None	None	N
A/N	0.6963	likely_pathogenic	0.7419	pathogenic	-0.319	Destabilizing	0.923	D	0.752	deleterious	None	None	None	None	N
A/P	0.9754	likely_pathogenic	0.9805	pathogenic	-0.155	Destabilizing	0.949	D	0.736	prob.delet.	D	0.546151749	None	None	N
A/Q	0.7896	likely_pathogenic	0.8224	pathogenic	-0.477	Destabilizing	0.923	D	0.733	prob.delet.	None	None	None	None	N
A/R	0.89	likely_pathogenic	0.9126	pathogenic	-0.282	Destabilizing	0.923	D	0.731	prob.delet.	None	None	None	None	N
A/S	0.1578	likely_benign	0.1732	benign	-0.645	Destabilizing	0.075	N	0.397	neutral	N	0.483935264	None	None	N
A/T	0.1335	likely_benign	0.1643	benign	-0.635	Destabilizing	0.008	N	0.409	neutral	D	0.536638567	None	None	N
A/V	0.146	likely_benign	0.2019	benign	-0.155	Destabilizing	0.075	N	0.389	neutral	N	0.512108269	None	None	N
A/W	0.9512	likely_pathogenic	0.9643	pathogenic	-0.869	Destabilizing	0.996	D	0.747	deleterious	None	None	None	None	N
A/Y	0.7735	likely_pathogenic	0.8242	pathogenic	-0.487	Destabilizing	0.987	D	0.774	deleterious	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.