TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9959	30100;30101;30102	chr2:178704597;178704596;178704595	chr2:179569324;179569323;179569322
N2AB	9642	29149;29150;29151	chr2:178704597;178704596;178704595	chr2:179569324;179569323;179569322
N2A	8715	26368;26369;26370	chr2:178704597;178704596;178704595	chr2:179569324;179569323;179569322
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-84
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.2332
• 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/T	None	None	0.001	None	0.307	0.335	0.24896430686	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6796	likely_pathogenic	0.6394	pathogenic	-1.072	Destabilizing	0.055	N	0.415	neutral	None	None	None	None	N
R/C	0.2625	likely_benign	0.266	benign	-1.069	Destabilizing	0.883	D	0.479	neutral	None	None	None	None	N
R/D	0.9405	likely_pathogenic	0.927	pathogenic	-0.277	Destabilizing	0.124	N	0.531	neutral	None	None	None	None	N
R/E	0.6202	likely_pathogenic	0.5937	pathogenic	-0.149	Destabilizing	0.055	N	0.476	neutral	None	None	None	None	N
R/F	0.7067	likely_pathogenic	0.6932	pathogenic	-0.863	Destabilizing	0.497	N	0.503	neutral	None	None	None	None	N
R/G	0.7112	likely_pathogenic	0.6735	pathogenic	-1.391	Destabilizing	0.081	N	0.486	neutral	None	None	None	None	N
R/H	0.1217	likely_benign	0.1146	benign	-1.535	Destabilizing	0.667	D	0.475	neutral	None	None	None	None	N
R/I	0.2898	likely_benign	0.2783	benign	-0.208	Destabilizing	0.001	N	0.433	neutral	None	None	None	None	N
R/K	0.1117	likely_benign	0.1097	benign	-1.193	Destabilizing	None	N	0.267	neutral	None	None	None	None	N
R/L	0.3581	ambiguous	0.3382	benign	-0.208	Destabilizing	0.02	N	0.449	neutral	None	None	None	None	N
R/M	0.4104	ambiguous	0.3865	ambiguous	-0.478	Destabilizing	0.497	N	0.494	neutral	None	None	None	None	N
R/N	0.8243	likely_pathogenic	0.7999	pathogenic	-0.612	Destabilizing	0.001	N	0.291	neutral	None	None	None	None	N
R/P	0.9958	likely_pathogenic	0.994	pathogenic	-0.477	Destabilizing	0.364	N	0.559	neutral	None	None	None	None	N
R/Q	0.1633	likely_benign	0.1558	benign	-0.791	Destabilizing	0.22	N	0.468	neutral	None	None	None	None	N
R/S	0.7475	likely_pathogenic	0.7157	pathogenic	-1.44	Destabilizing	0.042	N	0.469	neutral	None	None	None	None	N
R/T	0.3531	ambiguous	0.306	benign	-1.129	Destabilizing	0.001	N	0.307	neutral	None	None	None	None	N
R/V	0.4109	ambiguous	0.4005	ambiguous	-0.477	Destabilizing	0.02	N	0.454	neutral	None	None	None	None	N
R/W	0.3058	likely_benign	0.2865	benign	-0.445	Destabilizing	0.958	D	0.501	neutral	None	None	None	None	N
R/Y	0.5765	likely_pathogenic	0.5699	pathogenic	-0.177	Destabilizing	0.667	D	0.507	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.