TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7918	23977;23978;23979	chr2:178719740;178719739;178719738	chr2:179584467;179584466;179584465
N2AB	7601	23026;23027;23028	chr2:178719740;178719739;178719738	chr2:179584467;179584466;179584465
N2A	6674	20245;20246;20247	chr2:178719740;178719739;178719738	chr2:179584467;179584466;179584465
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-64
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.2563
• 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/F	rs767543848	-1.462	0.032	N	0.353	0.453	0.444706120422	gnomAD-2.1.1	1.79E-05	None	None	None	None	I	None	0	0	None	0	2.56226E-04	None	0	None	0	0	0
L/F	rs767543848	-1.462	0.032	N	0.353	0.453	0.444706120422	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	3.87297E-04	None	0	0	0	0	0
L/F	rs767543848	-1.462	0.032	N	0.353	0.453	0.444706120422	gnomAD-4.0.0	3.84394E-06	None	None	None	None	I	None	0	0	None	0	7.27696E-05	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
L/A	0.8316	likely_pathogenic	0.8255	pathogenic	-2.029	Highly Destabilizing	0.86	D	0.592	neutral	None	None	None	None	I
L/C	0.8802	likely_pathogenic	0.8937	pathogenic	-1.455	Destabilizing	0.998	D	0.628	neutral	None	None	None	None	I
L/D	0.9907	likely_pathogenic	0.9905	pathogenic	-0.997	Destabilizing	0.993	D	0.769	deleterious	None	None	None	None	I
L/E	0.9636	likely_pathogenic	0.9597	pathogenic	-0.911	Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	I
L/F	0.6247	likely_pathogenic	0.6373	pathogenic	-1.303	Destabilizing	0.032	N	0.353	neutral	N	0.488267358	None	None	I
L/G	0.9625	likely_pathogenic	0.9597	pathogenic	-2.448	Highly Destabilizing	0.978	D	0.763	deleterious	None	None	None	None	I
L/H	0.9295	likely_pathogenic	0.9316	pathogenic	-1.565	Destabilizing	0.997	D	0.718	prob.delet.	D	0.527869683	None	None	I
L/I	0.1712	likely_benign	0.1809	benign	-0.905	Destabilizing	0.126	N	0.301	neutral	D	0.523343983	None	None	I
L/K	0.9404	likely_pathogenic	0.9357	pathogenic	-1.27	Destabilizing	0.978	D	0.739	prob.delet.	None	None	None	None	I
L/M	0.337	likely_benign	0.3516	ambiguous	-0.835	Destabilizing	0.978	D	0.657	neutral	None	None	None	None	I
L/N	0.947	likely_pathogenic	0.9399	pathogenic	-1.184	Destabilizing	0.993	D	0.763	deleterious	None	None	None	None	I
L/P	0.5769	likely_pathogenic	0.6197	pathogenic	-1.251	Destabilizing	0.99	D	0.763	deleterious	N	0.416341443	None	None	I
L/Q	0.896	likely_pathogenic	0.8953	pathogenic	-1.238	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	I
L/R	0.9017	likely_pathogenic	0.9007	pathogenic	-0.813	Destabilizing	0.971	D	0.742	deleterious	D	0.527616193	None	None	I
L/S	0.9537	likely_pathogenic	0.9534	pathogenic	-2.009	Highly Destabilizing	0.978	D	0.739	prob.delet.	None	None	None	None	I
L/T	0.8416	likely_pathogenic	0.844	pathogenic	-1.778	Destabilizing	0.978	D	0.667	neutral	None	None	None	None	I
L/V	0.2129	likely_benign	0.2214	benign	-1.251	Destabilizing	0.489	N	0.527	neutral	N	0.505566299	None	None	I
L/W	0.8885	likely_pathogenic	0.8969	pathogenic	-1.357	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	I
L/Y	0.8967	likely_pathogenic	0.896	pathogenic	-1.142	Destabilizing	0.915	D	0.699	prob.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.