TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5482	16669;16670;16671	chr2:178732617;178732616;178732615	chr2:179597344;179597343;179597342
N2AB	5165	15718;15719;15720	chr2:178732617;178732616;178732615	chr2:179597344;179597343;179597342
N2A	4238	12937;12938;12939	chr2:178732617;178732616;178732615	chr2:179597344;179597343;179597342
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-38
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.5774
• 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	rs1261601154	None	0.055	N	0.581	0.348	0.434606191737	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/G	rs1261601154	None	0.055	N	0.581	0.348	0.434606191737	gnomAD-4.0.0	2.47918E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39065E-06	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	0.1868	likely_benign	0.2187	benign	-0.744	Destabilizing	0.016	N	0.515	neutral	None	None	None	None	N
R/C	0.1292	likely_benign	0.1198	benign	-0.758	Destabilizing	0.864	D	0.584	neutral	None	None	None	None	N
R/D	0.4857	ambiguous	0.5241	ambiguous	-0.06	Destabilizing	0.038	N	0.593	neutral	None	None	None	None	N
R/E	0.2118	likely_benign	0.2562	benign	0.101	Stabilizing	None	N	0.223	neutral	None	None	None	None	N
R/F	0.3957	ambiguous	0.4236	ambiguous	-0.436	Destabilizing	0.214	N	0.587	neutral	None	None	None	None	N
R/G	0.1313	likely_benign	0.1468	benign	-1.076	Destabilizing	0.055	N	0.581	neutral	N	0.488099093	None	None	N
R/H	0.0833	likely_benign	0.08	benign	-1.418	Destabilizing	0.356	N	0.605	neutral	None	None	None	None	N
R/I	0.1775	likely_benign	0.1989	benign	0.156	Stabilizing	0.093	N	0.609	neutral	N	0.488729977	None	None	N
R/K	0.0693	likely_benign	0.0821	benign	-0.604	Destabilizing	None	N	0.239	neutral	N	0.428545523	None	None	N
R/L	0.1516	likely_benign	0.1662	benign	0.156	Stabilizing	0.016	N	0.547	neutral	None	None	None	None	N
R/M	0.1622	likely_benign	0.1932	benign	-0.377	Destabilizing	0.007	N	0.361	neutral	None	None	None	None	N
R/N	0.3007	likely_benign	0.3485	ambiguous	-0.357	Destabilizing	0.072	N	0.571	neutral	None	None	None	None	N
R/P	0.8338	likely_pathogenic	0.8621	pathogenic	-0.123	Destabilizing	0.356	N	0.609	neutral	None	None	None	None	N
R/Q	0.0753	likely_benign	0.0812	benign	-0.377	Destabilizing	0.038	N	0.593	neutral	None	None	None	None	N
R/S	0.1866	likely_benign	0.2168	benign	-1.055	Destabilizing	0.012	N	0.543	neutral	N	0.408898182	None	None	N
R/T	0.0982	likely_benign	0.1138	benign	-0.693	Destabilizing	0.055	N	0.582	neutral	N	0.443378902	None	None	N
R/V	0.2107	likely_benign	0.2402	benign	-0.123	Destabilizing	0.038	N	0.595	neutral	None	None	None	None	N
R/W	0.1652	likely_benign	0.1754	benign	-0.141	Destabilizing	0.864	D	0.605	neutral	None	None	None	None	N
R/Y	0.2793	likely_benign	0.2947	benign	0.135	Stabilizing	0.628	D	0.591	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.