TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23078	69457;69458;69459	chr2:178577103;178577102;178577101	chr2:179441830;179441829;179441828
N2AB	21437	64534;64535;64536	chr2:178577103;178577102;178577101	chr2:179441830;179441829;179441828
N2A	20510	61753;61754;61755	chr2:178577103;178577102;178577101	chr2:179441830;179441829;179441828
N2B	14013	42262;42263;42264	chr2:178577103;178577102;178577101	chr2:179441830;179441829;179441828
Novex-1	14138	42637;42638;42639	chr2:178577103;178577102;178577101	chr2:179441830;179441829;179441828
Novex-2	14205	42838;42839;42840	chr2:178577103;178577102;178577101	chr2:179441830;179441829;179441828
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-55
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1143
• 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
E/G	rs761442590	-2.495	1.0	D	0.79	0.585	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	1.29199E-04	0	None	0	0	None	0	None	0	0	0
E/G	rs761442590	-2.495	1.0	D	0.79	0.585	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs761442590	-2.495	1.0	D	0.79	0.585	None	gnomAD-4.0.0	5.12786E-06	None	None	None	None	N	None	6.77209E-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
E/A	0.8902	likely_pathogenic	0.882	pathogenic	-1.604	Destabilizing	0.999	D	0.746	deleterious	D	0.538483113	None	None	N
E/C	0.985	likely_pathogenic	0.9859	pathogenic	-0.643	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/D	0.8414	likely_pathogenic	0.8293	pathogenic	-1.618	Destabilizing	0.999	D	0.681	prob.neutral	N	0.504503103	None	None	N
E/F	0.9924	likely_pathogenic	0.9934	pathogenic	-1.257	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
E/G	0.9276	likely_pathogenic	0.9213	pathogenic	-2.003	Highly Destabilizing	1.0	D	0.79	deleterious	D	0.54700549	None	None	N
E/H	0.9563	likely_pathogenic	0.9606	pathogenic	-1.075	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/I	0.9795	likely_pathogenic	0.9808	pathogenic	-0.45	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/K	0.9388	likely_pathogenic	0.9341	pathogenic	-1.349	Destabilizing	0.999	D	0.688	prob.neutral	D	0.523226014	None	None	N
E/L	0.9677	likely_pathogenic	0.9696	pathogenic	-0.45	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
E/M	0.9584	likely_pathogenic	0.9602	pathogenic	0.306	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
E/N	0.9741	likely_pathogenic	0.971	pathogenic	-1.587	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.822	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Q	0.4305	ambiguous	0.415	ambiguous	-1.291	Destabilizing	1.0	D	0.775	deleterious	N	0.503877496	None	None	N
E/R	0.9522	likely_pathogenic	0.9516	pathogenic	-1.201	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/S	0.8862	likely_pathogenic	0.8809	pathogenic	-2.261	Highly Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
E/T	0.9509	likely_pathogenic	0.951	pathogenic	-1.872	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/V	0.9359	likely_pathogenic	0.9391	pathogenic	-0.822	Destabilizing	1.0	D	0.787	deleterious	D	0.539243582	None	None	N
E/W	0.9943	likely_pathogenic	0.9953	pathogenic	-1.295	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/Y	0.9861	likely_pathogenic	0.9877	pathogenic	-1.038	Destabilizing	1.0	D	0.848	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.