TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7843	23752;23753;23754	chr2:178720115;178720114;178720113	chr2:179584842;179584841;179584840
N2AB	7526	22801;22802;22803	chr2:178720115;178720114;178720113	chr2:179584842;179584841;179584840
N2A	6599	20020;20021;20022	chr2:178720115;178720114;178720113	chr2:179584842;179584841;179584840
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-63
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.3423
• 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/M	None	None	0.602	N	0.346	0.252	0.258779203287	gnomAD-4.0.0	1.59144E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85878E-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	0.1803	likely_benign	0.1747	benign	-0.779	Destabilizing	0.055	N	0.325	neutral	None	None	None	None	I
R/C	0.1698	likely_benign	0.1669	benign	-0.721	Destabilizing	0.883	D	0.354	neutral	None	None	None	None	I
R/D	0.3426	ambiguous	0.339	benign	-0.266	Destabilizing	0.22	N	0.373	neutral	None	None	None	None	I
R/E	0.1802	likely_benign	0.1696	benign	-0.21	Destabilizing	0.055	N	0.311	neutral	None	None	None	None	I
R/F	0.3022	likely_benign	0.2766	benign	-1.047	Destabilizing	0.667	D	0.359	neutral	None	None	None	None	I
R/G	0.13	likely_benign	0.1288	benign	-0.99	Destabilizing	0.042	N	0.361	neutral	N	0.494811044	None	None	I
R/H	0.0758	likely_benign	0.0774	benign	-1.291	Destabilizing	0.667	D	0.367	neutral	None	None	None	None	I
R/I	0.1394	likely_benign	0.136	benign	-0.24	Destabilizing	0.497	N	0.369	neutral	None	None	None	None	I
R/K	0.0834	likely_benign	0.0749	benign	-0.775	Destabilizing	None	N	0.166	neutral	N	0.475509963	None	None	I
R/L	0.1543	likely_benign	0.1497	benign	-0.24	Destabilizing	0.22	N	0.372	neutral	None	None	None	None	I
R/M	0.1555	likely_benign	0.1449	benign	-0.288	Destabilizing	0.602	D	0.346	neutral	N	0.491848529	None	None	I
R/N	0.252	likely_benign	0.2398	benign	-0.184	Destabilizing	0.124	N	0.271	neutral	None	None	None	None	I
R/P	0.7635	likely_pathogenic	0.7671	pathogenic	-0.401	Destabilizing	0.364	N	0.376	neutral	None	None	None	None	I
R/Q	0.0775	likely_benign	0.076	benign	-0.528	Destabilizing	0.002	N	0.167	neutral	None	None	None	None	I
R/S	0.1801	likely_benign	0.1776	benign	-0.895	Destabilizing	0.001	N	0.209	neutral	N	0.467391912	None	None	I
R/T	0.1077	likely_benign	0.1055	benign	-0.7	Destabilizing	0.096	N	0.325	neutral	N	0.495637306	None	None	I
R/V	0.1796	likely_benign	0.1733	benign	-0.401	Destabilizing	0.22	N	0.39	neutral	None	None	None	None	I
R/W	0.1182	likely_benign	0.1122	benign	-0.817	Destabilizing	0.946	D	0.38	neutral	N	0.493887867	None	None	I
R/Y	0.2209	likely_benign	0.2002	benign	-0.461	Destabilizing	0.667	D	0.355	neutral	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.