TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5688	17287;17288;17289	chr2:178731813;178731812;178731811	chr2:179596540;179596539;179596538
N2AB	5371	16336;16337;16338	chr2:178731813;178731812;178731811	chr2:179596540;179596539;179596538
N2A	4444	13555;13556;13557	chr2:178731813;178731812;178731811	chr2:179596540;179596539;179596538
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-40
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4678
• 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	rs1314251790	-0.265	0.927	D	0.261	0.285	0.348764635752	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Q/H	rs1314251790	-0.265	0.927	D	0.261	0.285	0.348764635752	gnomAD-4.0.0	3.1825E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71677E-06	0	0
Q/L	None	None	0.27	N	0.265	0.305	0.488477830397	gnomAD-4.0.0	6.84205E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-05	0
Q/R	None	None	0.642	N	0.159	0.257	0.180583059064	gnomAD-4.0.0	1.36841E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79896E-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
Q/A	0.2192	likely_benign	0.2712	benign	-0.098	Destabilizing	0.013	N	0.114	neutral	None	None	None	None	N
Q/C	0.5929	likely_pathogenic	0.7406	pathogenic	0.044	Stabilizing	0.995	D	0.262	neutral	None	None	None	None	N
Q/D	0.2401	likely_benign	0.3131	benign	0.107	Stabilizing	0.003	N	0.115	neutral	None	None	None	None	N
Q/E	0.0677	likely_benign	0.0738	benign	0.074	Stabilizing	0.001	N	0.081	neutral	N	0.423022273	None	None	N
Q/F	0.6608	likely_pathogenic	0.7748	pathogenic	-0.388	Destabilizing	0.944	D	0.329	neutral	None	None	None	None	N
Q/G	0.2193	likely_benign	0.2815	benign	-0.253	Destabilizing	0.495	N	0.287	neutral	None	None	None	None	N
Q/H	0.163	likely_benign	0.2234	benign	-0.061	Destabilizing	0.927	D	0.261	neutral	D	0.523477269	None	None	N
Q/I	0.3821	ambiguous	0.4889	ambiguous	0.216	Stabilizing	0.543	D	0.341	neutral	None	None	None	None	N
Q/K	0.0796	likely_benign	0.0895	benign	0.078	Stabilizing	0.27	N	0.199	neutral	N	0.446976568	None	None	N
Q/L	0.1593	likely_benign	0.212	benign	0.216	Stabilizing	0.27	N	0.265	neutral	N	0.497541461	None	None	N
Q/M	0.377	ambiguous	0.4677	ambiguous	0.226	Stabilizing	0.944	D	0.257	neutral	None	None	None	None	N
Q/N	0.2305	likely_benign	0.304	benign	-0.243	Destabilizing	0.704	D	0.153	neutral	None	None	None	None	N
Q/P	0.2249	likely_benign	0.3885	ambiguous	0.139	Stabilizing	0.784	D	0.293	neutral	N	0.502024561	None	None	N
Q/R	0.0856	likely_benign	0.0987	benign	0.24	Stabilizing	0.642	D	0.159	neutral	N	0.48239865	None	None	N
Q/S	0.2237	likely_benign	0.2723	benign	-0.225	Destabilizing	0.329	N	0.187	neutral	None	None	None	None	N
Q/T	0.1756	likely_benign	0.2246	benign	-0.114	Destabilizing	0.013	N	0.137	neutral	None	None	None	None	N
Q/V	0.2625	likely_benign	0.3328	benign	0.139	Stabilizing	0.013	N	0.179	neutral	None	None	None	None	N
Q/W	0.4548	ambiguous	0.5984	pathogenic	-0.432	Destabilizing	0.995	D	0.261	neutral	None	None	None	None	N
Q/Y	0.4061	ambiguous	0.5322	ambiguous	-0.149	Destabilizing	0.981	D	0.338	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.