TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15861	47806;47807;47808	chr2:178617504;178617503;178617502	chr2:179482231;179482230;179482229
N2AB	14220	42883;42884;42885	chr2:178617504;178617503;178617502	chr2:179482231;179482230;179482229
N2A	13293	40102;40103;40104	chr2:178617504;178617503;178617502	chr2:179482231;179482230;179482229
N2B	6796	20611;20612;20613	chr2:178617504;178617503;178617502	chr2:179482231;179482230;179482229
Novex-1	6921	20986;20987;20988	chr2:178617504;178617503;178617502	chr2:179482231;179482230;179482229
Novex-2	6988	21187;21188;21189	chr2:178617504;178617503;178617502	chr2:179482231;179482230;179482229
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-3
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1442
• 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
S/C	rs2057561826	None	1.0	D	0.852	0.525	0.602958996521	gnomAD-4.0.0	5.01201E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.79564E-06	0	0
S/N	rs2057561467	None	0.999	D	0.783	0.287	0.317958651998	gnomAD-4.0.0	5.01315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.79667E-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
S/A	0.1589	likely_benign	0.1904	benign	-0.603	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
S/C	0.251	likely_benign	0.2977	benign	-0.571	Destabilizing	1.0	D	0.852	deleterious	D	0.67480621	None	None	N
S/D	0.6976	likely_pathogenic	0.7121	pathogenic	-1.112	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
S/E	0.8498	likely_pathogenic	0.8373	pathogenic	-1.064	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
S/F	0.4182	ambiguous	0.452	ambiguous	-0.608	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
S/G	0.1196	likely_benign	0.1302	benign	-0.904	Destabilizing	0.999	D	0.722	prob.delet.	N	0.49192899	None	None	N
S/H	0.7708	likely_pathogenic	0.7503	pathogenic	-1.454	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
S/I	0.556	ambiguous	0.6624	pathogenic	0.105	Stabilizing	1.0	D	0.855	deleterious	D	0.674040026	None	None	N
S/K	0.9644	likely_pathogenic	0.9615	pathogenic	-0.875	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
S/L	0.1727	likely_benign	0.2173	benign	0.105	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
S/M	0.3719	ambiguous	0.4249	ambiguous	0.336	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
S/N	0.4083	ambiguous	0.4616	ambiguous	-1.065	Destabilizing	0.999	D	0.783	deleterious	D	0.569154511	None	None	N
S/P	0.9004	likely_pathogenic	0.9178	pathogenic	-0.095	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
S/Q	0.8652	likely_pathogenic	0.8436	pathogenic	-1.14	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
S/R	0.9505	likely_pathogenic	0.9504	pathogenic	-0.857	Destabilizing	1.0	D	0.861	deleterious	D	0.633731468	None	None	N
S/T	0.1553	likely_benign	0.1987	benign	-0.889	Destabilizing	0.999	D	0.731	prob.delet.	D	0.532521139	None	None	N
S/V	0.5178	ambiguous	0.6096	pathogenic	-0.095	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
S/W	0.6948	likely_pathogenic	0.7023	pathogenic	-0.716	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
S/Y	0.4414	ambiguous	0.4544	ambiguous	-0.397	Destabilizing	1.0	D	0.869	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.