TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28094	84505;84506;84507	chr2:178561852;178561851;178561850	chr2:179426579;179426578;179426577
N2AB	26453	79582;79583;79584	chr2:178561852;178561851;178561850	chr2:179426579;179426578;179426577
N2A	25526	76801;76802;76803	chr2:178561852;178561851;178561850	chr2:179426579;179426578;179426577
N2B	19029	57310;57311;57312	chr2:178561852;178561851;178561850	chr2:179426579;179426578;179426577
Novex-1	19154	57685;57686;57687	chr2:178561852;178561851;178561850	chr2:179426579;179426578;179426577
Novex-2	19221	57886;57887;57888	chr2:178561852;178561851;178561850	chr2:179426579;179426578;179426577
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-92
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1983
• 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
K/N	rs746801951	-2.376	1.0	N	0.865	0.386	0.270001397563	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
K/N	rs746801951	-2.376	1.0	N	0.865	0.386	0.270001397563	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	0	None	0	2.77948E-05	None	0	0	0	0	0
K/R	None	None	0.999	N	0.723	0.274	0.414539908741	gnomAD-4.0.0	3.18337E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71706E-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
K/A	0.8969	likely_pathogenic	0.8745	pathogenic	-1.435	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
K/C	0.838	likely_pathogenic	0.8364	pathogenic	-1.551	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
K/D	0.9925	likely_pathogenic	0.9844	pathogenic	-2.558	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
K/E	0.7746	likely_pathogenic	0.6531	pathogenic	-2.229	Highly Destabilizing	0.999	D	0.744	deleterious	N	0.518782242	None	None	N
K/F	0.9647	likely_pathogenic	0.9568	pathogenic	-0.672	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
K/G	0.9364	likely_pathogenic	0.9126	pathogenic	-1.913	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/H	0.7551	likely_pathogenic	0.7088	pathogenic	-1.563	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
K/I	0.7791	likely_pathogenic	0.7485	pathogenic	-0.048	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
K/L	0.7203	likely_pathogenic	0.6997	pathogenic	-0.048	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/M	0.3511	ambiguous	0.3534	ambiguous	-0.465	Destabilizing	1.0	D	0.824	deleterious	N	0.512400978	None	None	N
K/N	0.9571	likely_pathogenic	0.9198	pathogenic	-2.169	Highly Destabilizing	1.0	D	0.865	deleterious	N	0.518782242	None	None	N
K/P	0.9987	likely_pathogenic	0.998	pathogenic	-0.495	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
K/Q	0.2725	likely_benign	0.2422	benign	-1.728	Destabilizing	1.0	D	0.864	deleterious	N	0.47450911	None	None	N
K/R	0.1285	likely_benign	0.1271	benign	-0.987	Destabilizing	0.999	D	0.723	prob.delet.	N	0.508648597	None	None	N
K/S	0.9262	likely_pathogenic	0.8956	pathogenic	-2.568	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
K/T	0.7627	likely_pathogenic	0.684	pathogenic	-1.984	Destabilizing	1.0	D	0.839	deleterious	N	0.50138555	None	None	N
K/V	0.7411	likely_pathogenic	0.7141	pathogenic	-0.495	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
K/W	0.9413	likely_pathogenic	0.9151	pathogenic	-0.815	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
K/Y	0.8563	likely_pathogenic	0.8333	pathogenic	-0.47	Destabilizing	1.0	D	0.863	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.