TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13883	41872;41873;41874	chr2:178635677;178635676;178635675	chr2:179500404;179500403;179500402
N2AB	12242	36949;36950;36951	chr2:178635677;178635676;178635675	chr2:179500404;179500403;179500402
N2A	11315	34168;34169;34170	chr2:178635677;178635676;178635675	chr2:179500404;179500403;179500402
N2B	4818	14677;14678;14679	chr2:178635677;178635676;178635675	chr2:179500404;179500403;179500402
Novex-1	4943	15052;15053;15054	chr2:178635677;178635676;178635675	chr2:179500404;179500403;179500402
Novex-2	5010	15253;15254;15255	chr2:178635677;178635676;178635675	chr2:179500404;179500403;179500402
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-89
• Domain position: 8
• Structural Position: 13
• Q(SASA): 0.3634
• 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/K	None	None	0.993	N	0.314	0.344	0.202086224978	gnomAD-4.0.0	1.62151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.05979E-05

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	0.6348	likely_pathogenic	0.6689	pathogenic	-0.826	Destabilizing	0.994	D	0.403	neutral	None	None	None	None	N
Q/C	0.9373	likely_pathogenic	0.9452	pathogenic	-0.134	Destabilizing	1.0	D	0.707	prob.delet.	None	None	None	None	N
Q/D	0.987	likely_pathogenic	0.9884	pathogenic	-0.953	Destabilizing	0.994	D	0.406	neutral	None	None	None	None	N
Q/E	0.3618	ambiguous	0.391	ambiguous	-0.757	Destabilizing	0.982	D	0.317	neutral	N	0.481775227	None	None	N
Q/F	0.9711	likely_pathogenic	0.9782	pathogenic	-0.296	Destabilizing	0.998	D	0.704	prob.delet.	None	None	None	None	N
Q/G	0.8972	likely_pathogenic	0.9126	pathogenic	-1.265	Destabilizing	0.994	D	0.505	neutral	None	None	None	None	N
Q/H	0.9102	likely_pathogenic	0.9252	pathogenic	-0.958	Destabilizing	0.998	D	0.542	neutral	D	0.522259625	None	None	N
Q/I	0.7357	likely_pathogenic	0.7454	pathogenic	0.345	Stabilizing	0.998	D	0.725	deleterious	None	None	None	None	N
Q/K	0.6022	likely_pathogenic	0.595	pathogenic	-0.345	Destabilizing	0.993	D	0.314	neutral	N	0.433965465	None	None	N
Q/L	0.5655	likely_pathogenic	0.6226	pathogenic	0.345	Stabilizing	0.993	D	0.505	neutral	N	0.468690657	None	None	N
Q/M	0.5855	likely_pathogenic	0.634	pathogenic	0.694	Stabilizing	0.998	D	0.547	neutral	None	None	None	None	N
Q/N	0.8841	likely_pathogenic	0.9022	pathogenic	-1.079	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	N
Q/P	0.984	likely_pathogenic	0.9838	pathogenic	-0.014	Destabilizing	0.998	D	0.621	neutral	D	0.522259625	None	None	N
Q/R	0.6301	likely_pathogenic	0.6227	pathogenic	-0.442	Destabilizing	0.993	D	0.402	neutral	N	0.480383976	None	None	N
Q/S	0.799	likely_pathogenic	0.8225	pathogenic	-1.268	Destabilizing	0.994	D	0.305	neutral	None	None	None	None	N
Q/T	0.6088	likely_pathogenic	0.652	pathogenic	-0.858	Destabilizing	0.998	D	0.577	neutral	None	None	None	None	N
Q/V	0.5829	likely_pathogenic	0.5882	pathogenic	-0.014	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	N
Q/W	0.9874	likely_pathogenic	0.9891	pathogenic	-0.203	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
Q/Y	0.9656	likely_pathogenic	0.9714	pathogenic	0.081	Stabilizing	0.998	D	0.559	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.