TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15859	47800;47801;47802	chr2:178617510;178617509;178617508	chr2:179482237;179482236;179482235
N2AB	14218	42877;42878;42879	chr2:178617510;178617509;178617508	chr2:179482237;179482236;179482235
N2A	13291	40096;40097;40098	chr2:178617510;178617509;178617508	chr2:179482237;179482236;179482235
N2B	6794	20605;20606;20607	chr2:178617510;178617509;178617508	chr2:179482237;179482236;179482235
Novex-1	6919	20980;20981;20982	chr2:178617510;178617509;178617508	chr2:179482237;179482236;179482235
Novex-2	6986	21181;21182;21183	chr2:178617510;178617509;178617508	chr2:179482237;179482236;179482235
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-3
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.2593
• 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
R/I	rs1209254347	-0.448	0.93	N	0.384	0.148	0.401753679984	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	0	0	None	0	3.82848E-04	None	0	None	0	0	0
R/I	rs1209254347	-0.448	0.93	N	0.384	0.148	0.401753679984	gnomAD-4.0.0	5.59316E-06	None	None	None	None	I	None	0	0	None	0	1.79046E-04	None	0	0	9.07166E-07	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
R/A	0.3115	likely_benign	0.3353	benign	-0.282	Destabilizing	0.505	D	0.42	neutral	None	None	None	None	I
R/C	0.1689	likely_benign	0.2145	benign	-0.404	Destabilizing	0.995	D	0.357	neutral	None	None	None	None	I
R/D	0.7325	likely_pathogenic	0.7757	pathogenic	-0.133	Destabilizing	0.712	D	0.364	neutral	None	None	None	None	I
R/E	0.3729	ambiguous	0.4075	ambiguous	-0.079	Destabilizing	0.553	D	0.397	neutral	None	None	None	None	I
R/F	0.533	ambiguous	0.5851	pathogenic	-0.541	Destabilizing	0.982	D	0.355	neutral	None	None	None	None	I
R/G	0.3082	likely_benign	0.3599	ambiguous	-0.465	Destabilizing	0.651	D	0.408	neutral	N	0.451414323	None	None	I
R/H	0.1467	likely_benign	0.1777	benign	-0.852	Destabilizing	0.982	D	0.403	neutral	None	None	None	None	I
R/I	0.1873	likely_benign	0.2252	benign	0.166	Stabilizing	0.93	D	0.384	neutral	N	0.450824488	None	None	I
R/K	0.0802	likely_benign	0.0875	benign	-0.345	Destabilizing	0.002	N	0.155	neutral	N	0.440566652	None	None	I
R/L	0.1879	likely_benign	0.2126	benign	0.166	Stabilizing	0.712	D	0.319	neutral	None	None	None	None	I
R/M	0.2089	likely_benign	0.2528	benign	-0.116	Destabilizing	0.982	D	0.402	neutral	None	None	None	None	I
R/N	0.571	likely_pathogenic	0.6448	pathogenic	-0.037	Destabilizing	0.712	D	0.465	neutral	None	None	None	None	I
R/P	0.2144	likely_benign	0.2145	benign	0.036	Stabilizing	0.003	N	0.138	neutral	None	None	None	None	I
R/Q	0.1194	likely_benign	0.1378	benign	-0.211	Destabilizing	0.712	D	0.489	neutral	None	None	None	None	I
R/S	0.4758	ambiguous	0.5361	ambiguous	-0.5	Destabilizing	0.651	D	0.481	neutral	N	0.440218962	None	None	I
R/T	0.2369	likely_benign	0.2871	benign	-0.316	Destabilizing	0.651	D	0.403	neutral	N	0.451396071	None	None	I
R/V	0.2605	likely_benign	0.2904	benign	0.036	Stabilizing	0.834	D	0.363	neutral	None	None	None	None	I
R/W	0.272	likely_benign	0.3197	benign	-0.519	Destabilizing	0.995	D	0.545	neutral	None	None	None	None	I
R/Y	0.4041	ambiguous	0.4617	ambiguous	-0.132	Destabilizing	0.982	D	0.387	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.