TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28737	86434;86435;86436	chr2:178559923;178559922;178559921	chr2:179424650;179424649;179424648
N2AB	27096	81511;81512;81513	chr2:178559923;178559922;178559921	chr2:179424650;179424649;179424648
N2A	26169	78730;78731;78732	chr2:178559923;178559922;178559921	chr2:179424650;179424649;179424648
N2B	19672	59239;59240;59241	chr2:178559923;178559922;178559921	chr2:179424650;179424649;179424648
Novex-1	19797	59614;59615;59616	chr2:178559923;178559922;178559921	chr2:179424650;179424649;179424648
Novex-2	19864	59815;59816;59817	chr2:178559923;178559922;178559921	chr2:179424650;179424649;179424648
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: Fn3-97
• Domain position: 87
• Structural Position: 121
• Q(SASA): 0.2141
• 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/N	None	None	0.994	D	0.861	0.499	0.558070701127	gnomAD-4.0.0	1.59146E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05

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	0.1387	likely_benign	0.1436	benign	-0.757	Destabilizing	0.693	D	0.775	deleterious	None	None	None	None	N
S/C	0.1857	likely_benign	0.1601	benign	-0.841	Destabilizing	0.056	N	0.757	deleterious	D	0.542863747	None	None	N
S/D	0.9746	likely_pathogenic	0.9655	pathogenic	-1.629	Destabilizing	0.996	D	0.838	deleterious	None	None	None	None	N
S/E	0.9755	likely_pathogenic	0.9689	pathogenic	-1.527	Destabilizing	0.996	D	0.846	deleterious	None	None	None	None	N
S/F	0.8595	likely_pathogenic	0.8529	pathogenic	-0.594	Destabilizing	0.987	D	0.881	deleterious	None	None	None	None	N
S/G	0.2596	likely_benign	0.2253	benign	-1.081	Destabilizing	0.944	D	0.811	deleterious	N	0.506121805	None	None	N
S/H	0.9455	likely_pathogenic	0.935	pathogenic	-1.467	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
S/I	0.6718	likely_pathogenic	0.637	pathogenic	0.03	Stabilizing	0.967	D	0.88	deleterious	D	0.535773403	None	None	N
S/K	0.9941	likely_pathogenic	0.9931	pathogenic	-0.886	Destabilizing	0.987	D	0.836	deleterious	None	None	None	None	N
S/L	0.467	ambiguous	0.4513	ambiguous	0.03	Stabilizing	0.845	D	0.855	deleterious	None	None	None	None	N
S/M	0.645	likely_pathogenic	0.6365	pathogenic	0.079	Stabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
S/N	0.8212	likely_pathogenic	0.7955	pathogenic	-1.28	Destabilizing	0.994	D	0.861	deleterious	D	0.553459584	None	None	N
S/P	0.9646	likely_pathogenic	0.9638	pathogenic	-0.198	Destabilizing	0.996	D	0.846	deleterious	None	None	None	None	N
S/Q	0.9544	likely_pathogenic	0.9503	pathogenic	-1.276	Destabilizing	0.996	D	0.85	deleterious	None	None	None	None	N
S/R	0.9852	likely_pathogenic	0.9827	pathogenic	-0.914	Destabilizing	0.994	D	0.845	deleterious	D	0.529986505	None	None	N
S/T	0.2478	likely_benign	0.227	benign	-1.018	Destabilizing	0.892	D	0.825	deleterious	N	0.518995366	None	None	N
S/V	0.5534	ambiguous	0.5062	ambiguous	-0.198	Destabilizing	0.975	D	0.866	deleterious	None	None	None	None	N
S/W	0.9292	likely_pathogenic	0.9268	pathogenic	-0.76	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
S/Y	0.8768	likely_pathogenic	0.8695	pathogenic	-0.405	Destabilizing	0.996	D	0.887	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.