TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9279	28060;28061;28062	chr2:178711995;178711994;178711993	chr2:179576722;179576721;179576720
N2AB	8962	27109;27110;27111	chr2:178711995;178711994;178711993	chr2:179576722;179576721;179576720
N2A	8035	24328;24329;24330	chr2:178711995;178711994;178711993	chr2:179576722;179576721;179576720
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-78
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0859
• 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
A/T	None	None	0.977	D	0.696	0.688	0.559502987721	gnomAD-4.0.0	1.36967E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80036E-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
A/C	0.9141	likely_pathogenic	0.9101	pathogenic	-1.54	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
A/D	0.9964	likely_pathogenic	0.9968	pathogenic	-2.426	Highly Destabilizing	0.999	D	0.867	deleterious	D	0.65037669	None	None	N
A/E	0.9917	likely_pathogenic	0.9916	pathogenic	-2.251	Highly Destabilizing	0.998	D	0.844	deleterious	None	None	None	None	N
A/F	0.9578	likely_pathogenic	0.966	pathogenic	-0.829	Destabilizing	0.998	D	0.887	deleterious	None	None	None	None	N
A/G	0.194	likely_benign	0.1918	benign	-1.768	Destabilizing	0.989	D	0.626	neutral	D	0.59053893	None	None	N
A/H	0.9974	likely_pathogenic	0.9978	pathogenic	-1.97	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/I	0.8183	likely_pathogenic	0.8208	pathogenic	-0.096	Destabilizing	0.966	D	0.76	deleterious	None	None	None	None	N
A/K	0.9981	likely_pathogenic	0.9981	pathogenic	-1.346	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
A/L	0.7912	likely_pathogenic	0.7661	pathogenic	-0.096	Destabilizing	0.966	D	0.698	prob.neutral	None	None	None	None	N
A/M	0.8644	likely_pathogenic	0.8694	pathogenic	-0.471	Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
A/N	0.9922	likely_pathogenic	0.9923	pathogenic	-1.6	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
A/P	0.9922	likely_pathogenic	0.9943	pathogenic	-0.458	Destabilizing	0.999	D	0.877	deleterious	D	0.634155524	None	None	N
A/Q	0.9894	likely_pathogenic	0.9886	pathogenic	-1.469	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
A/R	0.9935	likely_pathogenic	0.9938	pathogenic	-1.347	Destabilizing	0.998	D	0.868	deleterious	None	None	None	None	N
A/S	0.5143	ambiguous	0.5047	ambiguous	-2.049	Highly Destabilizing	0.989	D	0.633	neutral	D	0.612392768	None	None	N
A/T	0.6867	likely_pathogenic	0.6736	pathogenic	-1.749	Destabilizing	0.977	D	0.696	prob.neutral	D	0.608012	None	None	N
A/V	0.528	ambiguous	0.5369	ambiguous	-0.458	Destabilizing	0.235	N	0.404	neutral	N	0.502353277	None	None	N
A/W	0.9975	likely_pathogenic	0.9981	pathogenic	-1.478	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
A/Y	0.9899	likely_pathogenic	0.9922	pathogenic	-0.983	Destabilizing	0.999	D	0.892	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.