TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32032	96319;96320;96321	chr2:178544050;178544049;178544048	chr2:179408777;179408776;179408775
N2AB	30391	91396;91397;91398	chr2:178544050;178544049;178544048	chr2:179408777;179408776;179408775
N2A	29464	88615;88616;88617	chr2:178544050;178544049;178544048	chr2:179408777;179408776;179408775
N2B	22967	69124;69125;69126	chr2:178544050;178544049;178544048	chr2:179408777;179408776;179408775
Novex-1	23092	69499;69500;69501	chr2:178544050;178544049;178544048	chr2:179408777;179408776;179408775
Novex-2	23159	69700;69701;69702	chr2:178544050;178544049;178544048	chr2:179408777;179408776;179408775
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-153
• Domain position: 16
• Structural Position: 28
• Q(SASA): 0.1714
• 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
L/S	rs1267785229	-2.546	0.999	N	0.839	0.518	0.738826834845	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
L/S	rs1267785229	-2.546	0.999	N	0.839	0.518	0.738826834845	gnomAD-4.0.0	1.59166E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85902E-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
L/A	0.8744	likely_pathogenic	0.8494	pathogenic	-2.513	Highly Destabilizing	0.997	D	0.708	prob.delet.	None	None	None	None	I
L/C	0.8243	likely_pathogenic	0.7962	pathogenic	-1.925	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
L/D	0.9993	likely_pathogenic	0.9989	pathogenic	-2.558	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
L/E	0.9945	likely_pathogenic	0.9919	pathogenic	-2.326	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
L/F	0.5806	likely_pathogenic	0.4816	ambiguous	-1.518	Destabilizing	0.999	D	0.786	deleterious	N	0.50334906	None	None	I
L/G	0.9844	likely_pathogenic	0.978	pathogenic	-3.042	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
L/H	0.9854	likely_pathogenic	0.9756	pathogenic	-2.223	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
L/I	0.199	likely_benign	0.1823	benign	-0.985	Destabilizing	0.994	D	0.592	neutral	None	None	None	None	I
L/K	0.9908	likely_pathogenic	0.9864	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
L/M	0.2116	likely_benign	0.1998	benign	-0.949	Destabilizing	0.981	D	0.51	neutral	N	0.510603106	None	None	I
L/N	0.9941	likely_pathogenic	0.9916	pathogenic	-2.5	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
L/P	0.9943	likely_pathogenic	0.9903	pathogenic	-1.475	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
L/Q	0.9672	likely_pathogenic	0.9523	pathogenic	-2.339	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
L/R	0.9845	likely_pathogenic	0.9751	pathogenic	-1.804	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
L/S	0.9794	likely_pathogenic	0.969	pathogenic	-3.218	Highly Destabilizing	0.999	D	0.839	deleterious	N	0.506071768	None	None	I
L/T	0.9343	likely_pathogenic	0.9084	pathogenic	-2.823	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
L/V	0.2182	likely_benign	0.1916	benign	-1.475	Destabilizing	0.992	D	0.579	neutral	N	0.42093832	None	None	I
L/W	0.9658	likely_pathogenic	0.9309	pathogenic	-1.757	Destabilizing	1.0	D	0.824	deleterious	N	0.506578747	None	None	I
L/Y	0.9624	likely_pathogenic	0.9393	pathogenic	-1.505	Destabilizing	1.0	D	0.871	deleterious	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.