TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20003	60232;60233;60234	chr2:178591812;178591811;178591810	chr2:179456539;179456538;179456537
N2AB	18362	55309;55310;55311	chr2:178591812;178591811;178591810	chr2:179456539;179456538;179456537
N2A	17435	52528;52529;52530	chr2:178591812;178591811;178591810	chr2:179456539;179456538;179456537
N2B	10938	33037;33038;33039	chr2:178591812;178591811;178591810	chr2:179456539;179456538;179456537
Novex-1	11063	33412;33413;33414	chr2:178591812;178591811;178591810	chr2:179456539;179456538;179456537
Novex-2	11130	33613;33614;33615	chr2:178591812;178591811;178591810	chr2:179456539;179456538;179456537
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: Fn3-33
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.6449
• 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/C	rs1039014549	-0.049	1.0	N	0.749	0.453	0.403896168776	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
R/C	rs1039014549	-0.049	1.0	N	0.749	0.453	0.403896168776	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	2.94E-05	0	0
R/C	rs1039014549	-0.049	1.0	N	0.749	0.453	0.403896168776	gnomAD-4.0.0	9.91863E-06	None	None	None	None	I	None	8.01282E-05	0	None	0	0	None	0	0	5.93432E-06	3.29468E-05	0
R/G	rs1039014549	-0.337	1.0	N	0.575	0.421	0.358134431457	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
R/G	rs1039014549	-0.337	1.0	N	0.575	0.421	0.358134431457	gnomAD-4.0.0	1.36882E-06	None	None	None	None	I	None	0	2.23864E-05	None	0	0	None	0	0	8.99607E-07	0	0
R/H	rs756091180	-0.685	1.0	N	0.737	0.393	0.376216005999	gnomAD-2.1.1	1.79E-05	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	4E-05	1.57E-05	0
R/H	rs756091180	-0.685	1.0	N	0.737	0.393	0.376216005999	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	2.82486E-04	0	1.47E-05	0	0
R/H	rs756091180	-0.685	1.0	N	0.737	0.393	0.376216005999	gnomAD-4.0.0	2.41762E-05	None	None	None	None	I	None	4.00598E-05	0	None	0	0	None	1.09361E-04	0	2.11941E-05	3.2946E-05	1.60174E-05
R/P	None	None	1.0	N	0.686	0.391	0.401185642668	gnomAD-4.0.0	6.84407E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99612E-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	0.7947	likely_pathogenic	0.8258	pathogenic	0.001	Stabilizing	0.999	D	0.575	neutral	None	None	None	None	I
R/C	0.4893	ambiguous	0.5069	ambiguous	-0.017	Destabilizing	1.0	D	0.749	deleterious	N	0.469123378	None	None	I
R/D	0.8625	likely_pathogenic	0.8852	pathogenic	-0.084	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
R/E	0.682	likely_pathogenic	0.7242	pathogenic	-0.033	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	I
R/F	0.7923	likely_pathogenic	0.8114	pathogenic	-0.238	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
R/G	0.6497	likely_pathogenic	0.6718	pathogenic	-0.185	Destabilizing	1.0	D	0.575	neutral	N	0.498698175	None	None	I
R/H	0.2171	likely_benign	0.2236	benign	-0.675	Destabilizing	1.0	D	0.737	prob.delet.	N	0.454715325	None	None	I
R/I	0.6213	likely_pathogenic	0.6717	pathogenic	0.452	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
R/K	0.2974	likely_benign	0.3044	benign	-0.001	Destabilizing	0.998	D	0.463	neutral	None	None	None	None	I
R/L	0.6297	likely_pathogenic	0.6619	pathogenic	0.452	Stabilizing	1.0	D	0.575	neutral	N	0.474762523	None	None	I
R/M	0.6172	likely_pathogenic	0.6618	pathogenic	0.123	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
R/N	0.8088	likely_pathogenic	0.8199	pathogenic	0.317	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
R/P	0.9744	likely_pathogenic	0.9785	pathogenic	0.322	Stabilizing	1.0	D	0.686	prob.neutral	N	0.492233563	None	None	I
R/Q	0.2772	likely_benign	0.2899	benign	0.167	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
R/S	0.8	likely_pathogenic	0.8177	pathogenic	-0.038	Destabilizing	1.0	D	0.623	neutral	N	0.446133127	None	None	I
R/T	0.6243	likely_pathogenic	0.6686	pathogenic	0.138	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	I
R/V	0.7184	likely_pathogenic	0.7569	pathogenic	0.322	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
R/W	0.3349	likely_benign	0.3447	ambiguous	-0.286	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
R/Y	0.5917	likely_pathogenic	0.6106	pathogenic	0.12	Stabilizing	1.0	D	0.708	prob.delet.	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.