TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29716	89371;89372;89373	chr2:178553965;178553964;178553963	chr2:179418692;179418691;179418690
N2AB	28075	84448;84449;84450	chr2:178553965;178553964;178553963	chr2:179418692;179418691;179418690
N2A	27148	81667;81668;81669	chr2:178553965;178553964;178553963	chr2:179418692;179418691;179418690
N2B	20651	62176;62177;62178	chr2:178553965;178553964;178553963	chr2:179418692;179418691;179418690
Novex-1	20776	62551;62552;62553	chr2:178553965;178553964;178553963	chr2:179418692;179418691;179418690
Novex-2	20843	62752;62753;62754	chr2:178553965;178553964;178553963	chr2:179418692;179418691;179418690
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: Fn3-104
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.2959
• 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/P	rs1482572884	-0.412	None	N	0.29	0.094	0.144782658237	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.31E-05	None	0	0	0
Q/P	rs1482572884	-0.412	None	N	0.29	0.094	0.144782658237	gnomAD-4.0.0	1.60012E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4403E-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
Q/A	0.131	likely_benign	0.1255	benign	-0.692	Destabilizing	None	N	0.286	neutral	None	None	None	None	I
Q/C	0.4442	ambiguous	0.4294	ambiguous	-0.084	Destabilizing	0.245	N	0.578	neutral	None	None	None	None	I
Q/D	0.4827	ambiguous	0.4345	ambiguous	-0.1	Destabilizing	0.009	N	0.373	neutral	None	None	None	None	I
Q/E	0.1014	likely_benign	0.0879	benign	-0.005	Destabilizing	None	N	0.173	neutral	N	0.418407808	None	None	I
Q/F	0.4926	ambiguous	0.4716	ambiguous	-0.41	Destabilizing	0.022	N	0.563	neutral	None	None	None	None	I
Q/G	0.3278	likely_benign	0.3176	benign	-1.028	Destabilizing	0.004	N	0.512	neutral	None	None	None	None	I
Q/H	0.207	likely_benign	0.1952	benign	-0.654	Destabilizing	None	N	0.222	neutral	N	0.469434061	None	None	I
Q/I	0.1886	likely_benign	0.169	benign	0.156	Stabilizing	0.003	N	0.555	neutral	None	None	None	None	I
Q/K	0.1097	likely_benign	0.0982	benign	-0.179	Destabilizing	0.006	N	0.287	neutral	N	0.446018484	None	None	I
Q/L	0.0875	likely_benign	0.0787	benign	0.156	Stabilizing	None	N	0.377	neutral	N	0.374675674	None	None	I
Q/M	0.1918	likely_benign	0.1988	benign	0.409	Stabilizing	0.001	N	0.239	neutral	None	None	None	None	I
Q/N	0.262	likely_benign	0.2459	benign	-0.731	Destabilizing	0.009	N	0.36	neutral	None	None	None	None	I
Q/P	0.093	likely_benign	0.0777	benign	-0.096	Destabilizing	None	N	0.29	neutral	N	0.402035633	None	None	I
Q/R	0.1291	likely_benign	0.1144	benign	-0.077	Destabilizing	0.014	N	0.389	neutral	N	0.442516819	None	None	I
Q/S	0.1868	likely_benign	0.1781	benign	-0.88	Destabilizing	0.004	N	0.255	neutral	None	None	None	None	I
Q/T	0.1517	likely_benign	0.1437	benign	-0.582	Destabilizing	0.004	N	0.456	neutral	None	None	None	None	I
Q/V	0.1241	likely_benign	0.1092	benign	-0.096	Destabilizing	None	N	0.381	neutral	None	None	None	None	I
Q/W	0.572	likely_pathogenic	0.5215	ambiguous	-0.25	Destabilizing	0.788	D	0.561	neutral	None	None	None	None	I
Q/Y	0.3747	ambiguous	0.3475	ambiguous	-0.043	Destabilizing	0.022	N	0.484	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.