TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16784	50575;50576;50577	chr2:178612061;178612060;178612059	chr2:179476788;179476787;179476786
N2AB	15143	45652;45653;45654	chr2:178612061;178612060;178612059	chr2:179476788;179476787;179476786
N2A	14216	42871;42872;42873	chr2:178612061;178612060;178612059	chr2:179476788;179476787;179476786
N2B	7719	23380;23381;23382	chr2:178612061;178612060;178612059	chr2:179476788;179476787;179476786
Novex-1	7844	23755;23756;23757	chr2:178612061;178612060;178612059	chr2:179476788;179476787;179476786
Novex-2	7911	23956;23957;23958	chr2:178612061;178612060;178612059	chr2:179476788;179476787;179476786
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: Fn3-10
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4098
• 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/H	None	None	0.989	N	0.377	0.201	0.33085137897	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31252E-06	0	0
Q/R	rs765976576	0.164	0.891	N	0.267	0.146	0.183819452728	gnomAD-2.1.1	4.12E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.6909E-04
Q/R	rs765976576	0.164	0.891	N	0.267	0.146	0.183819452728	gnomAD-4.0.0	1.60291E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.04044E-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	0.2423	likely_benign	0.2296	benign	-0.483	Destabilizing	0.688	D	0.397	neutral	None	None	None	None	I
Q/C	0.6989	likely_pathogenic	0.6542	pathogenic	0.112	Stabilizing	0.998	D	0.328	neutral	None	None	None	None	I
Q/D	0.6211	likely_pathogenic	0.5878	pathogenic	-0.465	Destabilizing	0.971	D	0.319	neutral	None	None	None	None	I
Q/E	0.1188	likely_benign	0.1213	benign	-0.407	Destabilizing	0.911	D	0.307	neutral	N	0.438596439	None	None	I
Q/F	0.6999	likely_pathogenic	0.6928	pathogenic	-0.201	Destabilizing	0.949	D	0.371	neutral	None	None	None	None	I
Q/G	0.3552	ambiguous	0.3322	benign	-0.81	Destabilizing	0.971	D	0.34	neutral	None	None	None	None	I
Q/H	0.2802	likely_benign	0.263	benign	-0.77	Destabilizing	0.989	D	0.377	neutral	N	0.48325452	None	None	I
Q/I	0.2999	likely_benign	0.3051	benign	0.335	Stabilizing	0.728	D	0.372	neutral	None	None	None	None	I
Q/K	0.1315	likely_benign	0.1295	benign	-0.423	Destabilizing	0.891	D	0.269	neutral	N	0.434791918	None	None	I
Q/L	0.0964	likely_benign	0.0906	benign	0.335	Stabilizing	0.002	N	0.141	neutral	N	0.356719741	None	None	I
Q/M	0.3229	likely_benign	0.3029	benign	0.735	Stabilizing	0.949	D	0.378	neutral	None	None	None	None	I
Q/N	0.3326	likely_benign	0.3118	benign	-0.762	Destabilizing	0.971	D	0.343	neutral	None	None	None	None	I
Q/P	0.702	likely_pathogenic	0.6483	pathogenic	0.094	Stabilizing	0.989	D	0.39	neutral	N	0.477860013	None	None	I
Q/R	0.166	likely_benign	0.2036	benign	-0.352	Destabilizing	0.891	D	0.267	neutral	N	0.460676164	None	None	I
Q/S	0.2368	likely_benign	0.2233	benign	-0.816	Destabilizing	0.915	D	0.255	neutral	None	None	None	None	I
Q/T	0.1558	likely_benign	0.1503	benign	-0.583	Destabilizing	0.915	D	0.327	neutral	None	None	None	None	I
Q/V	0.2133	likely_benign	0.2013	benign	0.094	Stabilizing	0.525	D	0.327	neutral	None	None	None	None	I
Q/W	0.7171	likely_pathogenic	0.6978	pathogenic	-0.115	Destabilizing	0.998	D	0.33	neutral	None	None	None	None	I
Q/Y	0.5526	ambiguous	0.5332	ambiguous	0.08	Stabilizing	0.974	D	0.401	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.