TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25428	76507;76508;76509	chr2:178569850;178569849;178569848	chr2:179434577;179434576;179434575
N2AB	23787	71584;71585;71586	chr2:178569850;178569849;178569848	chr2:179434577;179434576;179434575
N2A	22860	68803;68804;68805	chr2:178569850;178569849;178569848	chr2:179434577;179434576;179434575
N2B	16363	49312;49313;49314	chr2:178569850;178569849;178569848	chr2:179434577;179434576;179434575
Novex-1	16488	49687;49688;49689	chr2:178569850;178569849;178569848	chr2:179434577;179434576;179434575
Novex-2	16555	49888;49889;49890	chr2:178569850;178569849;178569848	chr2:179434577;179434576;179434575
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-73
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.6695
• 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/R	rs1264945919	-0.143	0.892	N	0.557	0.205	0.210429274316	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
K/R	rs1264945919	-0.143	0.892	N	0.557	0.205	0.210429274316	gnomAD-4.0.0	1.59186E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.8831E-05	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	0.6254	likely_pathogenic	0.6127	pathogenic	-0.334	Destabilizing	0.916	D	0.601	neutral	None	None	None	None	N
K/C	0.838	likely_pathogenic	0.8362	pathogenic	-0.318	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
K/D	0.8909	likely_pathogenic	0.8835	pathogenic	-0.027	Destabilizing	0.975	D	0.694	prob.neutral	None	None	None	None	N
K/E	0.4558	ambiguous	0.4471	ambiguous	0.053	Stabilizing	0.892	D	0.511	neutral	N	0.495738015	None	None	N
K/F	0.9278	likely_pathogenic	0.9169	pathogenic	-0.226	Destabilizing	0.987	D	0.723	prob.delet.	None	None	None	None	N
K/G	0.7862	likely_pathogenic	0.7759	pathogenic	-0.642	Destabilizing	0.975	D	0.65	neutral	None	None	None	None	N
K/H	0.5246	ambiguous	0.5211	ambiguous	-0.967	Destabilizing	0.073	N	0.396	neutral	None	None	None	None	N
K/I	0.6752	likely_pathogenic	0.6524	pathogenic	0.435	Stabilizing	0.983	D	0.724	prob.delet.	N	0.489966792	None	None	N
K/L	0.6164	likely_pathogenic	0.5927	pathogenic	0.435	Stabilizing	0.975	D	0.645	neutral	None	None	None	None	N
K/M	0.5271	ambiguous	0.4985	ambiguous	0.191	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
K/N	0.799	likely_pathogenic	0.7891	pathogenic	-0.09	Destabilizing	0.967	D	0.655	neutral	N	0.497057136	None	None	N
K/P	0.5923	likely_pathogenic	0.5967	pathogenic	0.208	Stabilizing	0.996	D	0.724	prob.delet.	None	None	None	None	N
K/Q	0.2562	likely_benign	0.2528	benign	-0.145	Destabilizing	0.967	D	0.665	neutral	N	0.510784825	None	None	N
K/R	0.0925	likely_benign	0.0912	benign	-0.334	Destabilizing	0.892	D	0.557	neutral	N	0.46339631	None	None	N
K/S	0.7386	likely_pathogenic	0.728	pathogenic	-0.635	Destabilizing	0.916	D	0.595	neutral	None	None	None	None	N
K/T	0.4828	ambiguous	0.4463	ambiguous	-0.361	Destabilizing	0.983	D	0.687	prob.neutral	N	0.468317365	None	None	N
K/V	0.6047	likely_pathogenic	0.5849	pathogenic	0.208	Stabilizing	0.987	D	0.703	prob.neutral	None	None	None	None	N
K/W	0.9233	likely_pathogenic	0.9093	pathogenic	-0.185	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
K/Y	0.8456	likely_pathogenic	0.8323	pathogenic	0.122	Stabilizing	0.95	D	0.715	prob.delet.	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.