TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25362	76309;76310;76311	chr2:178570048;178570047;178570046	chr2:179434775;179434774;179434773
N2AB	23721	71386;71387;71388	chr2:178570048;178570047;178570046	chr2:179434775;179434774;179434773
N2A	22794	68605;68606;68607	chr2:178570048;178570047;178570046	chr2:179434775;179434774;179434773
N2B	16297	49114;49115;49116	chr2:178570048;178570047;178570046	chr2:179434775;179434774;179434773
Novex-1	16422	49489;49490;49491	chr2:178570048;178570047;178570046	chr2:179434775;179434774;179434773
Novex-2	16489	49690;49691;49692	chr2:178570048;178570047;178570046	chr2:179434775;179434774;179434773
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: Fn3-72
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.2403
• 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
L/F	None	None	0.988	N	0.754	0.352	0.452640719197	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
L/V	rs1409589701	None	0.919	N	0.565	0.165	0.300110245524	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93874E-04	None	0	0	0	0	0
L/V	rs1409589701	None	0.919	N	0.565	0.165	0.300110245524	gnomAD-4.0.0	6.58354E-06	None	None	None	None	N	None	0	0	None	0	1.93874E-04	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	0.5139	ambiguous	0.4668	ambiguous	-1.968	Destabilizing	0.968	D	0.627	neutral	None	None	None	None	N
L/C	0.591	likely_pathogenic	0.5619	ambiguous	-1.136	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/D	0.9072	likely_pathogenic	0.8614	pathogenic	-2.236	Highly Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
L/E	0.6459	likely_pathogenic	0.5693	pathogenic	-2.05	Highly Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	N
L/F	0.5017	ambiguous	0.4503	ambiguous	-1.16	Destabilizing	0.988	D	0.754	deleterious	N	0.484318025	None	None	N
L/G	0.6823	likely_pathogenic	0.6309	pathogenic	-2.426	Highly Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
L/H	0.5521	ambiguous	0.4744	ambiguous	-1.682	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/I	0.2504	likely_benign	0.2381	benign	-0.675	Destabilizing	0.938	D	0.509	neutral	None	None	None	None	N
L/K	0.4257	ambiguous	0.3544	ambiguous	-1.542	Destabilizing	0.991	D	0.758	deleterious	None	None	None	None	N
L/M	0.1559	likely_benign	0.1515	benign	-0.551	Destabilizing	0.825	D	0.421	neutral	N	0.473215209	None	None	N
L/N	0.4578	ambiguous	0.3737	ambiguous	-1.842	Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	N
L/P	0.572	likely_pathogenic	0.4959	ambiguous	-1.085	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
L/Q	0.2537	likely_benign	0.2193	benign	-1.783	Destabilizing	0.995	D	0.805	deleterious	None	None	None	None	N
L/R	0.3389	likely_benign	0.2528	benign	-1.179	Destabilizing	0.995	D	0.787	deleterious	None	None	None	None	N
L/S	0.6064	likely_pathogenic	0.5319	ambiguous	-2.438	Highly Destabilizing	0.988	D	0.749	deleterious	N	0.521807109	None	None	N
L/T	0.2134	likely_benign	0.1915	benign	-2.12	Highly Destabilizing	0.991	D	0.753	deleterious	None	None	None	None	N
L/V	0.1913	likely_benign	0.176	benign	-1.085	Destabilizing	0.919	D	0.565	neutral	N	0.469732489	None	None	N
L/W	0.6538	likely_pathogenic	0.5419	ambiguous	-1.483	Destabilizing	0.999	D	0.803	deleterious	N	0.514792543	None	None	N
L/Y	0.7024	likely_pathogenic	0.6245	pathogenic	-1.136	Destabilizing	0.995	D	0.799	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.