TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3279	10060;10061;10062	chr2:178764680;178764679;178764678	chr2:179629407;179629406;179629405
N2AB	3279	10060;10061;10062	chr2:178764680;178764679;178764678	chr2:179629407;179629406;179629405
N2A	3279	10060;10061;10062	chr2:178764680;178764679;178764678	chr2:179629407;179629406;179629405
N2B	3233	9922;9923;9924	chr2:178764680;178764679;178764678	chr2:179629407;179629406;179629405
Novex-1	3233	9922;9923;9924	chr2:178764680;178764679;178764678	chr2:179629407;179629406;179629405
Novex-2	3233	9922;9923;9924	chr2:178764680;178764679;178764678	chr2:179629407;179629406;179629405
Novex-3	3279	10060;10061;10062	chr2:178764680;178764679;178764678	chr2:179629407;179629406;179629405

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-23
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2595
• 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/V	None	None	0.999	D	0.499	0.455	0.694693139321	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.9496	likely_pathogenic	0.9725	pathogenic	-1.746	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
L/C	0.9658	likely_pathogenic	0.9829	pathogenic	-0.85	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
L/D	0.9988	likely_pathogenic	0.9994	pathogenic	-1.458	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
L/E	0.9891	likely_pathogenic	0.9951	pathogenic	-1.242	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
L/F	0.7692	likely_pathogenic	0.893	pathogenic	-0.961	Destabilizing	1.0	D	0.678	prob.neutral	D	0.652407507	None	None	I
L/G	0.9927	likely_pathogenic	0.997	pathogenic	-2.243	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
L/H	0.969	likely_pathogenic	0.989	pathogenic	-1.555	Destabilizing	1.0	D	0.778	deleterious	D	0.692577658	None	None	I
L/I	0.2326	likely_benign	0.2677	benign	-0.336	Destabilizing	0.999	D	0.487	neutral	N	0.514142107	None	None	I
L/K	0.9788	likely_pathogenic	0.9904	pathogenic	-1.029	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
L/M	0.5012	ambiguous	0.6107	pathogenic	-0.27	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
L/N	0.9928	likely_pathogenic	0.9967	pathogenic	-1.353	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
L/P	0.9811	likely_pathogenic	0.9933	pathogenic	-0.784	Destabilizing	1.0	D	0.787	deleterious	D	0.669631627	None	None	I
L/Q	0.9382	likely_pathogenic	0.9775	pathogenic	-1.187	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
L/R	0.9506	likely_pathogenic	0.9794	pathogenic	-0.908	Destabilizing	1.0	D	0.781	deleterious	D	0.646773929	None	None	I
L/S	0.9886	likely_pathogenic	0.9954	pathogenic	-2.066	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
L/T	0.9605	likely_pathogenic	0.981	pathogenic	-1.698	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
L/V	0.3457	ambiguous	0.4233	ambiguous	-0.784	Destabilizing	0.999	D	0.499	neutral	D	0.523340756	None	None	I
L/W	0.9542	likely_pathogenic	0.9846	pathogenic	-1.261	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
L/Y	0.9689	likely_pathogenic	0.988	pathogenic	-0.892	Destabilizing	1.0	D	0.763	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.