TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19923	59992;59993;59994	chr2:178592137;178592136;178592135	chr2:179456864;179456863;179456862
N2AB	18282	55069;55070;55071	chr2:178592137;178592136;178592135	chr2:179456864;179456863;179456862
N2A	17355	52288;52289;52290	chr2:178592137;178592136;178592135	chr2:179456864;179456863;179456862
N2B	10858	32797;32798;32799	chr2:178592137;178592136;178592135	chr2:179456864;179456863;179456862
Novex-1	10983	33172;33173;33174	chr2:178592137;178592136;178592135	chr2:179456864;179456863;179456862
Novex-2	11050	33373;33374;33375	chr2:178592137;178592136;178592135	chr2:179456864;179456863;179456862
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-32
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.7017
• Predicted PPI site: I

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
Q/H	rs2050348587	None	0.484	N	0.308	0.101	0.268660756437	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
Q/H	rs2050348587	None	0.484	N	0.308	0.101	0.268660756437	gnomAD-4.0.0	6.57947E-06	None	None	None	None	I	None	0	6.55566E-05	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
Q/A	0.136	likely_benign	0.1309	benign	-0.122	Destabilizing	0.035	N	0.342	neutral	None	None	None	None	I
Q/C	0.4725	ambiguous	0.4616	ambiguous	-0.103	Destabilizing	0.935	D	0.375	neutral	None	None	None	None	I
Q/D	0.2532	likely_benign	0.2317	benign	-0.102	Destabilizing	0.081	N	0.303	neutral	None	None	None	None	I
Q/E	0.081	likely_benign	0.0739	benign	-0.154	Destabilizing	None	N	0.207	neutral	N	0.447578709	None	None	I
Q/F	0.5023	ambiguous	0.4775	ambiguous	-0.519	Destabilizing	0.791	D	0.344	neutral	None	None	None	None	I
Q/G	0.2008	likely_benign	0.1879	benign	-0.233	Destabilizing	0.149	N	0.324	neutral	None	None	None	None	I
Q/H	0.1427	likely_benign	0.1345	benign	0.014	Stabilizing	0.484	N	0.308	neutral	N	0.446850777	None	None	I
Q/I	0.2307	likely_benign	0.2249	benign	0.072	Stabilizing	0.555	D	0.349	neutral	None	None	None	None	I
Q/K	0.0795	likely_benign	0.0786	benign	-0.001	Destabilizing	0.002	N	0.213	neutral	N	0.47338123	None	None	I
Q/L	0.1003	likely_benign	0.0965	benign	0.072	Stabilizing	0.117	N	0.329	neutral	N	0.474074664	None	None	I
Q/M	0.2695	likely_benign	0.2606	benign	0.057	Stabilizing	0.791	D	0.307	neutral	None	None	None	None	I
Q/N	0.1806	likely_benign	0.1721	benign	-0.282	Destabilizing	0.149	N	0.317	neutral	None	None	None	None	I
Q/P	0.2075	likely_benign	0.2057	benign	0.031	Stabilizing	0.484	N	0.325	neutral	N	0.504050854	None	None	I
Q/R	0.0909	likely_benign	0.0877	benign	0.223	Stabilizing	None	N	0.241	neutral	N	0.455411545	None	None	I
Q/S	0.1555	likely_benign	0.1499	benign	-0.264	Destabilizing	0.081	N	0.317	neutral	None	None	None	None	I
Q/T	0.1271	likely_benign	0.1214	benign	-0.189	Destabilizing	0.149	N	0.339	neutral	None	None	None	None	I
Q/V	0.1542	likely_benign	0.1503	benign	0.031	Stabilizing	0.149	N	0.343	neutral	None	None	None	None	I
Q/W	0.4544	ambiguous	0.4377	ambiguous	-0.585	Destabilizing	0.935	D	0.401	neutral	None	None	None	None	I
Q/Y	0.3238	likely_benign	0.3227	benign	-0.295	Destabilizing	0.791	D	0.311	neutral	None	None	None	None	I

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.