TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26852	80779;80780;80781	chr2:178565578;178565577;178565576	chr2:179430305;179430304;179430303
N2AB	25211	75856;75857;75858	chr2:178565578;178565577;178565576	chr2:179430305;179430304;179430303
N2A	24284	73075;73076;73077	chr2:178565578;178565577;178565576	chr2:179430305;179430304;179430303
N2B	17787	53584;53585;53586	chr2:178565578;178565577;178565576	chr2:179430305;179430304;179430303
Novex-1	17912	53959;53960;53961	chr2:178565578;178565577;178565576	chr2:179430305;179430304;179430303
Novex-2	17979	54160;54161;54162	chr2:178565578;178565577;178565576	chr2:179430305;179430304;179430303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-83
• Domain position: 73
• Structural Position: 107
• Q(SASA): 0.1148
• 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
R/C	rs185887755	-1.452	1.0	D	0.765	0.533	None	gnomAD-2.1.1	4.42472E-04	None	None	None	None	N	None	0	0	None	0	5.27934E-03	None	5.88312E-04	None	0	2.34E-05	0
R/C	rs185887755	-1.452	1.0	D	0.765	0.533	None	gnomAD-3.1.2	1.71023E-04	None	None	None	None	N	None	0	0	0	0	4.07292E-03	None	0	0	1.47E-05	8.285E-04	0
R/C	rs185887755	-1.452	1.0	D	0.765	0.533	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	3E-03	0	None	None	None	0	None
R/C	rs185887755	-1.452	1.0	D	0.765	0.533	None	gnomAD-4.0.0	1.63618E-04	None	None	None	None	N	None	1.33351E-05	1.66717E-05	None	0	4.39399E-03	None	0	0	1.01729E-05	5.05117E-04	1.12065E-04
R/H	rs202149931	-2.006	0.261	D	0.462	0.284	None	gnomAD-2.1.1	9.99E-05	None	None	None	None	N	None	5.78847E-04	5.66E-05	None	0	5.13E-05	None	0	None	0	7.8E-05	1.40331E-04
R/H	rs202149931	-2.006	0.261	D	0.462	0.284	None	gnomAD-3.1.2	1.77533E-04	None	None	None	None	N	None	5.06928E-04	0	0	0	0	None	0	0	8.82E-05	0	0
R/H	rs202149931	-2.006	0.261	D	0.462	0.284	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/H	rs202149931	-2.006	0.261	D	0.462	0.284	None	gnomAD-4.0.0	8.3664E-05	None	None	None	None	N	None	5.73318E-04	3.33367E-05	None	0	2.23015E-05	None	0	0	6.86654E-05	2.19592E-05	9.60523E-05
R/L	None	None	0.957	N	0.555	0.403	0.429552544315	gnomAD-4.0.0	6.84277E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15942E-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
R/A	0.7998	likely_pathogenic	0.5693	pathogenic	-1.633	Destabilizing	0.933	D	0.529	neutral	None	None	None	None	N
R/C	0.2775	likely_benign	0.1147	benign	-1.567	Destabilizing	1.0	D	0.765	deleterious	D	0.536791728	None	None	N
R/D	0.9879	likely_pathogenic	0.9636	pathogenic	-0.912	Destabilizing	0.99	D	0.603	neutral	None	None	None	None	N
R/E	0.8446	likely_pathogenic	0.6971	pathogenic	-0.701	Destabilizing	0.806	D	0.517	neutral	None	None	None	None	N
R/F	0.9114	likely_pathogenic	0.7276	pathogenic	-0.756	Destabilizing	0.987	D	0.745	deleterious	None	None	None	None	N
R/G	0.8418	likely_pathogenic	0.6038	pathogenic	-1.962	Destabilizing	0.982	D	0.534	neutral	D	0.554642493	None	None	N
R/H	0.2714	likely_benign	0.1556	benign	-1.845	Destabilizing	0.261	N	0.462	neutral	D	0.532018788	None	None	N
R/I	0.7227	likely_pathogenic	0.4476	ambiguous	-0.681	Destabilizing	0.988	D	0.739	prob.delet.	None	None	None	None	N
R/K	0.4215	ambiguous	0.2602	benign	-1.074	Destabilizing	0.406	N	0.573	neutral	None	None	None	None	N
R/L	0.6611	likely_pathogenic	0.3952	ambiguous	-0.681	Destabilizing	0.957	D	0.555	neutral	N	0.513914533	None	None	N
R/M	0.7382	likely_pathogenic	0.48	ambiguous	-1.259	Destabilizing	0.997	D	0.649	neutral	None	None	None	None	N
R/N	0.9411	likely_pathogenic	0.8299	pathogenic	-1.149	Destabilizing	0.965	D	0.475	neutral	None	None	None	None	N
R/P	0.9969	likely_pathogenic	0.9941	pathogenic	-0.988	Destabilizing	0.997	D	0.667	neutral	D	0.555149472	None	None	N
R/Q	0.178	likely_benign	0.1067	benign	-0.924	Destabilizing	0.388	N	0.489	neutral	None	None	None	None	N
R/S	0.8649	likely_pathogenic	0.6482	pathogenic	-1.881	Destabilizing	0.964	D	0.506	neutral	N	0.510365679	None	None	N
R/T	0.7914	likely_pathogenic	0.5408	ambiguous	-1.476	Destabilizing	0.965	D	0.537	neutral	None	None	None	None	N
R/V	0.7702	likely_pathogenic	0.5183	ambiguous	-0.988	Destabilizing	0.967	D	0.67	neutral	None	None	None	None	N
R/W	0.54	ambiguous	0.3595	ambiguous	-0.413	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
R/Y	0.8001	likely_pathogenic	0.5503	ambiguous	-0.247	Destabilizing	0.975	D	0.667	neutral	None	None	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.