TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9628	29107;29108;29109	chr2:178707685;178707684;178707683	chr2:179572412;179572411;179572410
N2AB	9311	28156;28157;28158	chr2:178707685;178707684;178707683	chr2:179572412;179572411;179572410
N2A	8384	25375;25376;25377	chr2:178707685;178707684;178707683	chr2:179572412;179572411;179572410
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: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-82
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.5688
• 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	None	None	0.549	None	0.416	0.21	0.43848807779	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
R/W	rs1286102161	None	0.99	None	0.505	0.489	0.466486631293	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/W	rs1286102161	None	0.99	None	0.505	0.489	0.466486631293	gnomAD-4.0.0	6.56927E-06	None	None	None	None	N	None	2.41173E-05	0	None	0	0	None	0	0	0	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	0.6392	likely_pathogenic	0.4685	ambiguous	0.011	Stabilizing	0.25	N	0.42	neutral	None	None	None	None	N
R/C	0.4784	ambiguous	0.3374	benign	-0.205	Destabilizing	0.992	D	0.437	neutral	None	None	None	None	N
R/D	0.8511	likely_pathogenic	0.7632	pathogenic	-0.257	Destabilizing	0.617	D	0.407	neutral	None	None	None	None	N
R/E	0.5097	ambiguous	0.4058	ambiguous	-0.221	Destabilizing	0.25	N	0.419	neutral	None	None	None	None	N
R/F	0.7646	likely_pathogenic	0.6481	pathogenic	-0.303	Destabilizing	0.972	D	0.417	neutral	None	None	None	None	N
R/G	0.4612	ambiguous	0.2953	benign	-0.127	Destabilizing	0.549	D	0.416	neutral	None	None	None	None	N
R/H	0.1796	likely_benign	0.1485	benign	-0.576	Destabilizing	0.92	D	0.389	neutral	None	None	None	None	N
R/I	0.4566	ambiguous	0.3361	benign	0.328	Stabilizing	0.92	D	0.422	neutral	None	None	None	None	N
R/K	0.1006	likely_benign	0.0972	benign	-0.132	Destabilizing	0.001	N	0.18	neutral	None	None	None	None	N
R/L	0.4668	ambiguous	0.3439	ambiguous	0.328	Stabilizing	0.617	D	0.416	neutral	None	None	None	None	N
R/M	0.4348	ambiguous	0.3102	benign	-0.047	Destabilizing	0.963	D	0.399	neutral	None	None	None	None	N
R/N	0.7461	likely_pathogenic	0.6284	pathogenic	0.007	Stabilizing	0.617	D	0.397	neutral	None	None	None	None	N
R/P	0.9484	likely_pathogenic	0.8881	pathogenic	0.24	Stabilizing	0.92	D	0.416	neutral	None	None	None	None	N
R/Q	0.1442	likely_benign	0.1155	benign	-0.063	Destabilizing	0.447	N	0.433	neutral	None	None	None	None	N
R/S	0.7033	likely_pathogenic	0.5503	ambiguous	-0.213	Destabilizing	0.379	N	0.415	neutral	None	None	None	None	N
R/T	0.4371	ambiguous	0.3038	benign	-0.072	Destabilizing	0.549	D	0.411	neutral	None	None	None	None	N
R/V	0.5374	ambiguous	0.4193	ambiguous	0.24	Stabilizing	0.85	D	0.39	neutral	None	None	None	None	N
R/W	0.3369	likely_benign	0.2406	benign	-0.462	Destabilizing	0.99	D	0.505	neutral	None	None	None	None	N
R/Y	0.6587	likely_pathogenic	0.5698	pathogenic	-0.06	Destabilizing	0.972	D	0.42	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.