TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9435	28528;28529;28530	chr2:178710794;178710793;178710792	chr2:179575521;179575520;179575519
N2AB	9118	27577;27578;27579	chr2:178710794;178710793;178710792	chr2:179575521;179575520;179575519
N2A	8191	24796;24797;24798	chr2:178710794;178710793;178710792	chr2:179575521;179575520;179575519
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-80
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.452
• 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/G	rs1355846496	-0.825	0.081	None	0.302	0.211	0.42526943336	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/G	rs1355846496	-0.825	0.081	None	0.302	0.211	0.42526943336	gnomAD-4.0.0	1.59099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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	0.3258	likely_benign	0.345	ambiguous	0.002	Stabilizing	0.025	N	0.283	neutral	None	None	None	None	N
R/C	0.3191	likely_benign	0.3174	benign	-0.157	Destabilizing	0.958	D	0.257	neutral	None	None	None	None	N
R/D	0.6384	likely_pathogenic	0.6521	pathogenic	-0.196	Destabilizing	0.22	N	0.321	neutral	None	None	None	None	N
R/E	0.3196	likely_benign	0.3097	benign	-0.148	Destabilizing	0.025	N	0.195	neutral	None	None	None	None	N
R/F	0.5533	ambiguous	0.5915	pathogenic	-0.274	Destabilizing	0.667	D	0.333	neutral	None	None	None	None	N
R/G	0.2252	likely_benign	0.2357	benign	-0.164	Destabilizing	0.081	N	0.302	neutral	None	None	None	None	N
R/H	0.1196	likely_benign	0.1334	benign	-0.656	Destabilizing	0.001	N	0.245	neutral	None	None	None	None	N
R/I	0.2479	likely_benign	0.2556	benign	0.401	Stabilizing	0.003	N	0.289	neutral	None	None	None	None	N
R/K	0.0769	likely_benign	0.0795	benign	-0.114	Destabilizing	None	N	0.151	neutral	None	None	None	None	N
R/L	0.2293	likely_benign	0.2601	benign	0.401	Stabilizing	0.055	N	0.301	neutral	None	None	None	None	N
R/M	0.2387	likely_benign	0.248	benign	0.02	Stabilizing	0.667	D	0.292	neutral	None	None	None	None	N
R/N	0.4634	ambiguous	0.5012	ambiguous	0.081	Stabilizing	0.104	N	0.181	neutral	None	None	None	None	N
R/P	0.8197	likely_pathogenic	0.8609	pathogenic	0.287	Stabilizing	0.364	N	0.377	neutral	None	None	None	None	N
R/Q	0.0965	likely_benign	0.0999	benign	-0.01	Destabilizing	0.004	N	0.203	neutral	None	None	None	None	N
R/S	0.3931	ambiguous	0.403	ambiguous	-0.194	Destabilizing	0.042	N	0.293	neutral	None	None	None	None	N
R/T	0.1898	likely_benign	0.1885	benign	-0.028	Destabilizing	0.081	N	0.298	neutral	None	None	None	None	N
R/V	0.309	likely_benign	0.3182	benign	0.287	Stabilizing	0.055	N	0.304	neutral	None	None	None	None	N
R/W	0.1972	likely_benign	0.22	benign	-0.384	Destabilizing	0.958	D	0.263	neutral	None	None	None	None	N
R/Y	0.4778	ambiguous	0.5099	ambiguous	0.025	Stabilizing	0.22	N	0.352	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.