TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30363	91312;91313;91314	chr2:178551813;178551812;178551811	chr2:179416540;179416539;179416538
N2AB	28722	86389;86390;86391	chr2:178551813;178551812;178551811	chr2:179416540;179416539;179416538
N2A	27795	83608;83609;83610	chr2:178551813;178551812;178551811	chr2:179416540;179416539;179416538
N2B	21298	64117;64118;64119	chr2:178551813;178551812;178551811	chr2:179416540;179416539;179416538
Novex-1	21423	64492;64493;64494	chr2:178551813;178551812;178551811	chr2:179416540;179416539;179416538
Novex-2	21490	64693;64694;64695	chr2:178551813;178551812;178551811	chr2:179416540;179416539;179416538
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: Fn3-109
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2696
• 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	rs762103106	None	1.0	N	0.829	0.39	0.306053231325	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs762103106	None	1.0	N	0.829	0.39	0.306053231325	gnomAD-4.0.0	6.5741E-06	None	None	None	None	N	None	2.41324E-05	0	None	0	0	None	0	0	0	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	0.831	likely_pathogenic	0.8653	pathogenic	-1.455	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
K/C	0.6665	likely_pathogenic	0.6935	pathogenic	-1.593	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
K/D	0.9871	likely_pathogenic	0.9908	pathogenic	-2.437	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/E	0.7332	likely_pathogenic	0.7545	pathogenic	-2.111	Highly Destabilizing	0.999	D	0.74	deleterious	N	0.491955028	None	None	N
K/F	0.8635	likely_pathogenic	0.8942	pathogenic	-0.581	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
K/G	0.8903	likely_pathogenic	0.9147	pathogenic	-1.941	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/H	0.5376	ambiguous	0.5904	pathogenic	-1.707	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/I	0.6606	likely_pathogenic	0.7074	pathogenic	-0.052	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
K/L	0.5978	likely_pathogenic	0.6647	pathogenic	-0.052	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/M	0.351	ambiguous	0.3544	ambiguous	-0.499	Destabilizing	1.0	D	0.777	deleterious	N	0.498663677	None	None	N
K/N	0.9251	likely_pathogenic	0.9402	pathogenic	-2.175	Highly Destabilizing	1.0	D	0.829	deleterious	N	0.483561237	None	None	N
K/P	0.9976	likely_pathogenic	0.9987	pathogenic	-0.503	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/Q	0.2404	likely_benign	0.2415	benign	-1.723	Destabilizing	1.0	D	0.833	deleterious	D	0.523887408	None	None	N
K/R	0.0802	likely_benign	0.0908	benign	-1.17	Destabilizing	0.999	D	0.717	prob.delet.	N	0.438076578	None	None	N
K/S	0.8815	likely_pathogenic	0.901	pathogenic	-2.587	Highly Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
K/T	0.6718	likely_pathogenic	0.7218	pathogenic	-2.01	Highly Destabilizing	1.0	D	0.815	deleterious	N	0.465341624	None	None	N
K/V	0.5959	likely_pathogenic	0.6499	pathogenic	-0.503	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
K/W	0.7998	likely_pathogenic	0.847	pathogenic	-0.749	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/Y	0.6739	likely_pathogenic	0.7185	pathogenic	-0.403	Destabilizing	1.0	D	0.818	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.