TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7853	23782;23783;23784	chr2:178720085;178720084;178720083	chr2:179584812;179584811;179584810
N2AB	7536	22831;22832;22833	chr2:178720085;178720084;178720083	chr2:179584812;179584811;179584810
N2A	6609	20050;20051;20052	chr2:178720085;178720084;178720083	chr2:179584812;179584811;179584810
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-63
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.0692
• 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	rs776061262	-1.688	0.988	D	0.806	0.609	0.685073295601	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.89E-06	0
L/F	rs776061262	-1.688	0.988	D	0.806	0.609	0.685073295601	gnomAD-4.0.0	3.18285E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	3.02462E-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
L/A	0.9625	likely_pathogenic	0.9483	pathogenic	-2.424	Highly Destabilizing	0.976	D	0.745	deleterious	None	None	None	None	N
L/C	0.9519	likely_pathogenic	0.9355	pathogenic	-1.893	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.225	Highly Destabilizing	1.0	D	0.941	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.9976	pathogenic	-2.911	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/F	0.5562	ambiguous	0.525	ambiguous	-1.481	Destabilizing	0.988	D	0.806	deleterious	D	0.551159087	None	None	N
L/G	0.9932	likely_pathogenic	0.9918	pathogenic	-3.04	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/H	0.9904	likely_pathogenic	0.991	pathogenic	-2.798	Highly Destabilizing	1.0	D	0.918	deleterious	D	0.579685049	None	None	N
L/I	0.3041	likely_benign	0.2818	benign	-0.592	Destabilizing	0.235	N	0.65	neutral	D	0.55376598	None	None	N
L/K	0.9949	likely_pathogenic	0.9953	pathogenic	-1.881	Destabilizing	0.998	D	0.911	deleterious	None	None	None	None	N
L/M	0.389	ambiguous	0.3447	ambiguous	-0.8	Destabilizing	0.971	D	0.78	deleterious	None	None	None	None	N
L/N	0.9982	likely_pathogenic	0.9984	pathogenic	-2.553	Highly Destabilizing	1.0	D	0.942	deleterious	None	None	None	None	N
L/P	0.998	likely_pathogenic	0.9981	pathogenic	-1.191	Destabilizing	1.0	D	0.933	deleterious	D	0.579685049	None	None	N
L/Q	0.9867	likely_pathogenic	0.9869	pathogenic	-2.226	Highly Destabilizing	1.0	D	0.942	deleterious	None	None	None	None	N
L/R	0.9867	likely_pathogenic	0.988	pathogenic	-1.956	Destabilizing	1.0	D	0.938	deleterious	D	0.579685049	None	None	N
L/S	0.9955	likely_pathogenic	0.9948	pathogenic	-3.155	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/T	0.9886	likely_pathogenic	0.9863	pathogenic	-2.666	Highly Destabilizing	0.988	D	0.84	deleterious	None	None	None	None	N
L/V	0.3504	ambiguous	0.3354	benign	-1.191	Destabilizing	0.007	N	0.409	neutral	D	0.541702113	None	None	N
L/W	0.9561	likely_pathogenic	0.9575	pathogenic	-1.928	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/Y	0.9617	likely_pathogenic	0.9572	pathogenic	-1.62	Destabilizing	0.964	D	0.861	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.