TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26027	78304;78305;78306	chr2:178568053;178568052;178568051	chr2:179432780;179432779;179432778
N2AB	24386	73381;73382;73383	chr2:178568053;178568052;178568051	chr2:179432780;179432779;179432778
N2A	23459	70600;70601;70602	chr2:178568053;178568052;178568051	chr2:179432780;179432779;179432778
N2B	16962	51109;51110;51111	chr2:178568053;178568052;178568051	chr2:179432780;179432779;179432778
Novex-1	17087	51484;51485;51486	chr2:178568053;178568052;178568051	chr2:179432780;179432779;179432778
Novex-2	17154	51685;51686;51687	chr2:178568053;178568052;178568051	chr2:179432780;179432779;179432778
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-77
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0741
• 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
L/P	rs773883465	-2.26	1.0	D	0.838	0.715	0.842886931792	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.94E-06	0
L/P	rs773883465	-2.26	1.0	D	0.838	0.715	0.842886931792	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs773883465	-2.26	1.0	D	0.838	0.715	0.842886931792	gnomAD-4.0.0	1.48767E-05	None	None	None	None	N	None	1.33565E-05	0	None	0	0	None	0	0	1.78026E-05	0	3.2039E-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
L/A	0.8433	likely_pathogenic	0.8404	pathogenic	-3.204	Highly Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
L/C	0.8488	likely_pathogenic	0.8469	pathogenic	-2.115	Highly Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.493	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/E	0.9973	likely_pathogenic	0.9973	pathogenic	-3.217	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/F	0.8404	likely_pathogenic	0.8369	pathogenic	-1.925	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
L/G	0.9906	likely_pathogenic	0.9902	pathogenic	-3.692	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/H	0.9956	likely_pathogenic	0.9956	pathogenic	-3.102	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/I	0.088	likely_benign	0.0759	benign	-1.691	Destabilizing	0.999	D	0.524	neutral	None	None	None	None	N
L/K	0.9967	likely_pathogenic	0.9967	pathogenic	-2.595	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/M	0.3283	likely_benign	0.33	benign	-1.827	Destabilizing	1.0	D	0.694	prob.neutral	D	0.528509368	None	None	N
L/N	0.9979	likely_pathogenic	0.9979	pathogenic	-3.276	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/P	0.9967	likely_pathogenic	0.9967	pathogenic	-2.196	Highly Destabilizing	1.0	D	0.838	deleterious	D	0.523055566	None	None	N
L/Q	0.9907	likely_pathogenic	0.9907	pathogenic	-2.953	Highly Destabilizing	1.0	D	0.821	deleterious	D	0.523055566	None	None	N
L/R	0.9928	likely_pathogenic	0.9928	pathogenic	-2.548	Highly Destabilizing	1.0	D	0.809	deleterious	D	0.523055566	None	None	N
L/S	0.9888	likely_pathogenic	0.9884	pathogenic	-3.661	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/T	0.8932	likely_pathogenic	0.89	pathogenic	-3.256	Highly Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
L/V	0.0857	likely_benign	0.0738	benign	-2.196	Highly Destabilizing	0.999	D	0.565	neutral	N	0.40707052	None	None	N
L/W	0.9906	likely_pathogenic	0.9902	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
L/Y	0.9904	likely_pathogenic	0.9905	pathogenic	-2.126	Highly Destabilizing	1.0	D	0.751	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.