TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17685	53278;53279;53280	chr2:178607635;178607634;178607633	chr2:179472362;179472361;179472360
N2AB	16044	48355;48356;48357	chr2:178607635;178607634;178607633	chr2:179472362;179472361;179472360
N2A	15117	45574;45575;45576	chr2:178607635;178607634;178607633	chr2:179472362;179472361;179472360
N2B	8620	26083;26084;26085	chr2:178607635;178607634;178607633	chr2:179472362;179472361;179472360
Novex-1	8745	26458;26459;26460	chr2:178607635;178607634;178607633	chr2:179472362;179472361;179472360
Novex-2	8812	26659;26660;26661	chr2:178607635;178607634;178607633	chr2:179472362;179472361;179472360
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-113
• Domain position: 9
• Structural Position: 18
• Q(SASA): 0.5798
• 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
M/I	rs200387466	0.171	0.017	N	0.209	0.177	0.493156425868	gnomAD-2.1.1	2.04339E-04	None	None	None	None	I	None	2.27668E-03	2.83E-05	None	0	0	None	0	None	0	0	1.40726E-04
M/I	rs200387466	0.171	0.017	N	0.209	0.177	0.493156425868	gnomAD-3.1.2	6.71088E-04	None	None	None	None	I	None	2.38992E-03	1.96747E-04	0	0	0	None	0	0	0	0	0
M/I	rs200387466	0.171	0.017	N	0.209	0.177	0.493156425868	1000 genomes	7.98722E-04	None	None	None	None	I	None	3E-03	0	None	None	0	0	None	None	None	0	None
M/I	rs200387466	0.171	0.017	N	0.209	0.177	0.493156425868	gnomAD-4.0.0	1.27707E-04	None	None	None	None	I	None	2.49413E-03	8.33667E-05	None	0	0	None	0	0	3.3916E-06	0	1.60159E-04
M/K	None	None	0.101	N	0.405	0.236	0.552205712323	gnomAD-4.0.0	3.18548E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72181E-06	0	0
M/T	rs1289030052	None	0.003	N	0.231	0.189	0.723229803861	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
M/T	rs1289030052	None	0.003	N	0.231	0.189	0.723229803861	gnomAD-4.0.0	6.41157E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.19764E-05	0	0
M/V	rs2055217957	None	0.001	N	0.183	0.085	0.39619538035	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
M/V	rs2055217957	None	0.001	N	0.183	0.085	0.39619538035	gnomAD-4.0.0	6.81979E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.64636E-04	8.47902E-06	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
M/A	0.392	ambiguous	0.3602	ambiguous	-0.54	Destabilizing	0.061	N	0.297	neutral	None	None	None	None	I
M/C	0.7011	likely_pathogenic	0.6841	pathogenic	-0.702	Destabilizing	0.836	D	0.409	neutral	None	None	None	None	I
M/D	0.8881	likely_pathogenic	0.8959	pathogenic	0.377	Stabilizing	0.593	D	0.483	neutral	None	None	None	None	I
M/E	0.5201	ambiguous	0.5407	ambiguous	0.355	Stabilizing	0.228	N	0.43	neutral	None	None	None	None	I
M/F	0.3783	ambiguous	0.3715	ambiguous	0.035	Stabilizing	0.418	N	0.29	neutral	None	None	None	None	I
M/G	0.7458	likely_pathogenic	0.7328	pathogenic	-0.753	Destabilizing	0.375	N	0.443	neutral	None	None	None	None	I
M/H	0.482	ambiguous	0.4793	ambiguous	0.176	Stabilizing	0.94	D	0.446	neutral	None	None	None	None	I
M/I	0.3726	ambiguous	0.3805	ambiguous	-0.058	Destabilizing	0.017	N	0.209	neutral	N	0.437415722	None	None	I
M/K	0.1764	likely_benign	0.1843	benign	0.276	Stabilizing	0.101	N	0.405	neutral	N	0.343388053	None	None	I
M/L	0.1194	likely_benign	0.1012	benign	-0.058	Destabilizing	None	N	0.173	neutral	N	0.41255735	None	None	I
M/N	0.5806	likely_pathogenic	0.578	pathogenic	0.313	Stabilizing	0.593	D	0.455	neutral	None	None	None	None	I
M/P	0.574	likely_pathogenic	0.5783	pathogenic	-0.189	Destabilizing	0.816	D	0.492	neutral	None	None	None	None	I
M/Q	0.2302	likely_benign	0.2308	benign	0.211	Stabilizing	0.418	N	0.285	neutral	None	None	None	None	I
M/R	0.1854	likely_benign	0.2051	benign	0.754	Stabilizing	0.001	N	0.23	neutral	N	0.349468664	None	None	I
M/S	0.5186	ambiguous	0.5118	ambiguous	-0.196	Destabilizing	0.129	N	0.411	neutral	None	None	None	None	I
M/T	0.2375	likely_benign	0.2527	benign	-0.108	Destabilizing	0.003	N	0.231	neutral	N	0.424697141	None	None	I
M/V	0.1007	likely_benign	0.1049	benign	-0.189	Destabilizing	0.001	N	0.183	neutral	N	0.404284583	None	None	I
M/W	0.6756	likely_pathogenic	0.6838	pathogenic	0.038	Stabilizing	0.983	D	0.404	neutral	None	None	None	None	I
M/Y	0.5928	likely_pathogenic	0.5855	pathogenic	0.162	Stabilizing	0.593	D	0.435	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.