TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9424	28495;28496;28497	chr2:178710827;178710826;178710825	chr2:179575554;179575553;179575552
N2AB	9107	27544;27545;27546	chr2:178710827;178710826;178710825	chr2:179575554;179575553;179575552
N2A	8180	24763;24764;24765	chr2:178710827;178710826;178710825	chr2:179575554;179575553;179575552
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: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-80
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.8913
• 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
Q/K	rs748778927	0.3	0.27	None	0.317	0.279	0.193865811164	gnomAD-2.1.1	7.13E-06	None	None	None	None	I	None	4.13E-05	0	None	0	0	None	0	None	0	7.8E-06	0
Q/K	rs748778927	0.3	0.27	None	0.317	0.279	0.193865811164	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Q/K	rs748778927	0.3	0.27	None	0.317	0.279	0.193865811164	gnomAD-4.0.0	4.33777E-06	None	None	None	None	I	None	5.34045E-05	0	None	0	0	None	0	0	2.54274E-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	0.1653	likely_benign	0.2028	benign	-0.154	Destabilizing	0.013	N	0.103	neutral	None	None	None	None	I
Q/C	0.7722	likely_pathogenic	0.8544	pathogenic	0.051	Stabilizing	0.981	D	0.337	neutral	None	None	None	None	I
Q/D	0.4025	ambiguous	0.4903	ambiguous	-0.041	Destabilizing	0.543	D	0.33	neutral	None	None	None	None	I
Q/E	0.0959	likely_benign	0.0937	benign	-0.083	Destabilizing	0.01	N	0.115	neutral	None	None	None	None	I
Q/F	0.622	likely_pathogenic	0.7449	pathogenic	-0.436	Destabilizing	0.893	D	0.423	neutral	None	None	None	None	I
Q/G	0.275	likely_benign	0.34	benign	-0.307	Destabilizing	0.495	N	0.277	neutral	None	None	None	None	I
Q/H	0.265	likely_benign	0.3329	benign	-0.123	Destabilizing	0.927	D	0.411	neutral	None	None	None	None	I
Q/I	0.3695	ambiguous	0.4742	ambiguous	0.157	Stabilizing	0.329	N	0.306	neutral	None	None	None	None	I
Q/K	0.1066	likely_benign	0.1268	benign	0.032	Stabilizing	0.27	N	0.317	neutral	None	None	None	None	I
Q/L	0.1236	likely_benign	0.1458	benign	0.157	Stabilizing	0.002	N	0.103	neutral	None	None	None	None	I
Q/M	0.3457	ambiguous	0.4242	ambiguous	0.262	Stabilizing	0.085	N	0.223	neutral	None	None	None	None	I
Q/N	0.3184	likely_benign	0.3967	ambiguous	-0.281	Destabilizing	0.704	D	0.395	neutral	None	None	None	None	I
Q/P	0.0991	likely_benign	0.1553	benign	0.08	Stabilizing	0.784	D	0.456	neutral	None	None	None	None	I
Q/R	0.1178	likely_benign	0.1442	benign	0.229	Stabilizing	0.006	N	0.173	neutral	None	None	None	None	I
Q/S	0.1874	likely_benign	0.2712	benign	-0.258	Destabilizing	0.329	N	0.323	neutral	None	None	None	None	I
Q/T	0.2119	likely_benign	0.2762	benign	-0.158	Destabilizing	0.495	N	0.316	neutral	None	None	None	None	I
Q/V	0.2349	likely_benign	0.3079	benign	0.08	Stabilizing	0.013	N	0.125	neutral	None	None	None	None	I
Q/W	0.5569	ambiguous	0.6784	pathogenic	-0.456	Destabilizing	0.995	D	0.321	neutral	None	None	None	None	I
Q/Y	0.4375	ambiguous	0.5611	ambiguous	-0.187	Destabilizing	0.981	D	0.433	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.