TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10055	30388;30389;30390	chr2:178704207;178704206;178704205	chr2:179568934;179568933;179568932
N2AB	9738	29437;29438;29439	chr2:178704207;178704206;178704205	chr2:179568934;179568933;179568932
N2A	8811	26656;26657;26658	chr2:178704207;178704206;178704205	chr2:179568934;179568933;179568932
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-85
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.3503
• 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
Q/H	rs1560511850	None	0.939	None	0.491	0.256	0.288352970974	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
Q/H	rs1560511850	None	0.939	None	0.491	0.256	0.288352970974	gnomAD-4.0.0	1.59092E-06	None	None	None	None	N	None	0	0	None	0	2.77254E-05	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
Q/A	0.3495	ambiguous	0.4413	ambiguous	-0.645	Destabilizing	0.037	N	0.269	neutral	None	None	None	None	N
Q/C	0.922	likely_pathogenic	0.9562	pathogenic	-0.026	Destabilizing	0.996	D	0.543	neutral	None	None	None	None	N
Q/D	0.8235	likely_pathogenic	0.9134	pathogenic	-0.618	Destabilizing	0.59	D	0.446	neutral	None	None	None	None	N
Q/E	0.11	likely_benign	0.131	benign	-0.529	Destabilizing	0.007	N	0.156	neutral	None	None	None	None	N
Q/F	0.9448	likely_pathogenic	0.9729	pathogenic	-0.36	Destabilizing	0.984	D	0.549	neutral	None	None	None	None	N
Q/G	0.5472	ambiguous	0.6966	pathogenic	-1.0	Destabilizing	0.742	D	0.507	neutral	None	None	None	None	N
Q/H	0.6083	likely_pathogenic	0.79	pathogenic	-0.862	Destabilizing	0.939	D	0.491	neutral	None	None	None	None	N
Q/I	0.7774	likely_pathogenic	0.8167	pathogenic	0.255	Stabilizing	0.953	D	0.581	neutral	None	None	None	None	N
Q/K	0.2482	likely_benign	0.2991	benign	-0.387	Destabilizing	0.309	N	0.457	neutral	None	None	None	None	N
Q/L	0.4974	ambiguous	0.6259	pathogenic	0.255	Stabilizing	0.684	D	0.514	neutral	None	None	None	None	N
Q/M	0.6014	likely_pathogenic	0.6747	pathogenic	0.716	Stabilizing	0.984	D	0.491	neutral	None	None	None	None	N
Q/N	0.6693	likely_pathogenic	0.7893	pathogenic	-0.939	Destabilizing	0.742	D	0.491	neutral	None	None	None	None	N
Q/P	0.9254	likely_pathogenic	0.9681	pathogenic	-0.013	Destabilizing	0.007	N	0.303	neutral	None	None	None	None	N
Q/R	0.2538	likely_benign	0.3308	benign	-0.306	Destabilizing	0.684	D	0.491	neutral	None	None	None	None	N
Q/S	0.4912	ambiguous	0.6262	pathogenic	-1.013	Destabilizing	0.373	N	0.438	neutral	None	None	None	None	N
Q/T	0.4744	ambiguous	0.5733	pathogenic	-0.729	Destabilizing	0.742	D	0.498	neutral	None	None	None	None	N
Q/V	0.6337	likely_pathogenic	0.7208	pathogenic	-0.013	Destabilizing	0.742	D	0.537	neutral	None	None	None	None	N
Q/W	0.924	likely_pathogenic	0.9608	pathogenic	-0.238	Destabilizing	0.996	D	0.585	neutral	None	None	None	None	N
Q/Y	0.8899	likely_pathogenic	0.9486	pathogenic	-0.02	Destabilizing	0.984	D	0.565	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.