TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9460	28603;28604;28605	chr2:178710719;178710718;178710717	chr2:179575446;179575445;179575444
N2AB	9143	27652;27653;27654	chr2:178710719;178710718;178710717	chr2:179575446;179575445;179575444
N2A	8216	24871;24872;24873	chr2:178710719;178710718;178710717	chr2:179575446;179575445;179575444
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-80
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.3758
• 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
D/H	None	None	0.996	None	0.562	0.29	0.435915822735	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85793E-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
D/A	0.2971	likely_benign	0.3535	ambiguous	-0.239	Destabilizing	0.896	D	0.553	neutral	None	None	None	None	N
D/C	0.8269	likely_pathogenic	0.8723	pathogenic	-0.03	Destabilizing	0.159	N	0.487	neutral	None	None	None	None	N
D/E	0.2272	likely_benign	0.2698	benign	-0.268	Destabilizing	0.103	N	0.279	neutral	None	None	None	None	N
D/F	0.7696	likely_pathogenic	0.8371	pathogenic	0.124	Stabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	N
D/G	0.2148	likely_benign	0.2364	benign	-0.504	Destabilizing	0.811	D	0.479	neutral	None	None	None	None	N
D/H	0.4585	ambiguous	0.5634	ambiguous	0.246	Stabilizing	0.996	D	0.562	neutral	None	None	None	None	N
D/I	0.6459	likely_pathogenic	0.7536	pathogenic	0.427	Stabilizing	0.988	D	0.699	prob.neutral	None	None	None	None	N
D/K	0.5879	likely_pathogenic	0.6768	pathogenic	0.338	Stabilizing	0.919	D	0.502	neutral	None	None	None	None	N
D/L	0.5654	likely_pathogenic	0.6789	pathogenic	0.427	Stabilizing	0.976	D	0.627	neutral	None	None	None	None	N
D/M	0.8	likely_pathogenic	0.8687	pathogenic	0.534	Stabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
D/N	0.1464	likely_benign	0.1646	benign	-0.228	Destabilizing	0.059	N	0.252	neutral	None	None	None	None	N
D/P	0.9213	likely_pathogenic	0.9534	pathogenic	0.229	Stabilizing	0.996	D	0.555	neutral	None	None	None	None	N
D/Q	0.4573	ambiguous	0.5884	pathogenic	-0.115	Destabilizing	0.976	D	0.52	neutral	None	None	None	None	N
D/R	0.5826	likely_pathogenic	0.6674	pathogenic	0.563	Stabilizing	0.976	D	0.661	neutral	None	None	None	None	N
D/S	0.1743	likely_benign	0.2015	benign	-0.332	Destabilizing	0.851	D	0.448	neutral	None	None	None	None	N
D/T	0.3823	ambiguous	0.4523	ambiguous	-0.106	Destabilizing	0.919	D	0.502	neutral	None	None	None	None	N
D/V	0.4458	ambiguous	0.5419	ambiguous	0.229	Stabilizing	0.968	D	0.679	prob.neutral	None	None	None	None	N
D/W	0.9373	likely_pathogenic	0.9637	pathogenic	0.326	Stabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
D/Y	0.4484	ambiguous	0.554	ambiguous	0.388	Stabilizing	0.995	D	0.702	prob.neutral	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.