TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6064	18415;18416;18417	chr2:178730210;178730209;178730208	chr2:179594937;179594936;179594935
N2AB	5747	17464;17465;17466	chr2:178730210;178730209;178730208	chr2:179594937;179594936;179594935
N2A	4820	14683;14684;14685	chr2:178730210;178730209;178730208	chr2:179594937;179594936;179594935
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-44
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.7633
• 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
D/H	rs750822862	-0.317	0.901	N	0.55	0.189	0.156986980423	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	3.27E-05	None	0	0	0
D/H	rs750822862	-0.317	0.901	N	0.55	0.189	0.156986980423	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
D/H	rs750822862	-0.317	0.901	N	0.55	0.189	0.156986980423	gnomAD-4.0.0	3.8449E-06	None	None	None	None	N	None	3.38375E-05	0	None	0	0	None	0	0	0	1.3403E-05	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
D/A	0.1349	likely_benign	0.1353	benign	0.012	Stabilizing	0.722	D	0.487	neutral	N	0.447186346	None	None	N
D/C	0.6089	likely_pathogenic	0.5936	pathogenic	0.333	Stabilizing	0.996	D	0.661	neutral	None	None	None	None	N
D/E	0.1169	likely_benign	0.1213	benign	-0.122	Destabilizing	0.008	N	0.116	neutral	N	0.459710139	None	None	N
D/F	0.5233	ambiguous	0.5164	ambiguous	-0.167	Destabilizing	0.987	D	0.607	neutral	None	None	None	None	N
D/G	0.115	likely_benign	0.1176	benign	-0.145	Destabilizing	0.565	D	0.474	neutral	N	0.433616829	None	None	N
D/H	0.2402	likely_benign	0.2397	benign	-0.008	Destabilizing	0.901	D	0.55	neutral	N	0.509658957	None	None	N
D/I	0.3	likely_benign	0.2799	benign	0.362	Stabilizing	0.961	D	0.597	neutral	None	None	None	None	N
D/K	0.2663	likely_benign	0.2761	benign	0.548	Stabilizing	0.633	D	0.476	neutral	None	None	None	None	N
D/L	0.3345	likely_benign	0.3308	benign	0.362	Stabilizing	0.923	D	0.568	neutral	None	None	None	None	N
D/M	0.5049	ambiguous	0.5019	ambiguous	0.474	Stabilizing	0.996	D	0.611	neutral	None	None	None	None	N
D/N	0.0748	likely_benign	0.0735	benign	0.444	Stabilizing	0.003	N	0.115	neutral	N	0.452245449	None	None	N
D/P	0.5177	ambiguous	0.5392	ambiguous	0.268	Stabilizing	0.961	D	0.545	neutral	None	None	None	None	N
D/Q	0.2506	likely_benign	0.2636	benign	0.45	Stabilizing	0.858	D	0.452	neutral	None	None	None	None	N
D/R	0.3089	likely_benign	0.3214	benign	0.598	Stabilizing	0.923	D	0.542	neutral	None	None	None	None	N
D/S	0.0939	likely_benign	0.096	benign	0.321	Stabilizing	0.633	D	0.411	neutral	None	None	None	None	N
D/T	0.1875	likely_benign	0.1851	benign	0.436	Stabilizing	0.775	D	0.511	neutral	None	None	None	None	N
D/V	0.2036	likely_benign	0.1906	benign	0.268	Stabilizing	0.949	D	0.592	neutral	N	0.493574783	None	None	N
D/W	0.8587	likely_pathogenic	0.8579	pathogenic	-0.151	Destabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	N
D/Y	0.2342	likely_benign	0.2284	benign	0.052	Stabilizing	0.983	D	0.61	neutral	N	0.456492263	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.