TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5005	15238;15239;15240	chr2:178734911;178734910;178734909	chr2:179599638;179599637;179599636
N2AB	4688	14287;14288;14289	chr2:178734911;178734910;178734909	chr2:179599638;179599637;179599636
N2A	3761	11506;11507;11508	chr2:178734911;178734910;178734909	chr2:179599638;179599637;179599636
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-33
• Domain position: 25
• Structural Position: 35
• Q(SASA): 0.1179
• 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/V	rs1449279284	-0.967	0.006	N	0.255	0.163	0.0846915920261	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.04E-06	0
L/V	rs1449279284	-0.967	0.006	N	0.255	0.163	0.0846915920261	gnomAD-4.0.0	1.3694E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79972E-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	0.8655	likely_pathogenic	0.8385	pathogenic	-2.327	Highly Destabilizing	0.559	D	0.709	prob.delet.	None	None	None	None	N
L/C	0.8942	likely_pathogenic	0.8691	pathogenic	-1.565	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
L/D	0.9985	likely_pathogenic	0.9984	pathogenic	-1.9	Destabilizing	0.993	D	0.852	deleterious	None	None	None	None	N
L/E	0.9858	likely_pathogenic	0.9864	pathogenic	-1.674	Destabilizing	0.978	D	0.843	deleterious	None	None	None	None	N
L/F	0.5434	ambiguous	0.5278	ambiguous	-1.327	Destabilizing	0.956	D	0.765	deleterious	None	None	None	None	N
L/G	0.9748	likely_pathogenic	0.9732	pathogenic	-2.882	Highly Destabilizing	0.978	D	0.836	deleterious	None	None	None	None	N
L/H	0.9761	likely_pathogenic	0.9753	pathogenic	-2.217	Highly Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	N
L/I	0.1119	likely_benign	0.095	benign	-0.736	Destabilizing	0.008	N	0.255	neutral	None	None	None	None	N
L/K	0.9859	likely_pathogenic	0.9866	pathogenic	-1.55	Destabilizing	0.978	D	0.813	deleterious	None	None	None	None	N
L/M	0.2271	likely_benign	0.2251	benign	-0.698	Destabilizing	0.942	D	0.739	prob.delet.	N	0.507032506	None	None	N
L/N	0.9883	likely_pathogenic	0.9874	pathogenic	-1.811	Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	N
L/P	0.987	likely_pathogenic	0.9863	pathogenic	-1.245	Destabilizing	0.99	D	0.85	deleterious	N	0.470002358	None	None	N
L/Q	0.9528	likely_pathogenic	0.955	pathogenic	-1.647	Destabilizing	0.99	D	0.807	deleterious	N	0.512114899	None	None	N
L/R	0.9696	likely_pathogenic	0.9704	pathogenic	-1.365	Destabilizing	0.97	D	0.809	deleterious	N	0.512114899	None	None	N
L/S	0.9721	likely_pathogenic	0.964	pathogenic	-2.642	Highly Destabilizing	0.956	D	0.791	deleterious	None	None	None	None	N
L/T	0.8754	likely_pathogenic	0.8556	pathogenic	-2.257	Highly Destabilizing	0.86	D	0.765	deleterious	None	None	None	None	N
L/V	0.1154	likely_benign	0.1029	benign	-1.245	Destabilizing	0.006	N	0.255	neutral	N	0.303510907	None	None	N
L/W	0.9134	likely_pathogenic	0.9147	pathogenic	-1.609	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
L/Y	0.9364	likely_pathogenic	0.9342	pathogenic	-1.325	Destabilizing	0.978	D	0.803	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.