TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30889	92890;92891;92892	chr2:178548961;178548960;178548959	chr2:179413688;179413687;179413686
N2AB	29248	87967;87968;87969	chr2:178548961;178548960;178548959	chr2:179413688;179413687;179413686
N2A	28321	85186;85187;85188	chr2:178548961;178548960;178548959	chr2:179413688;179413687;179413686
N2B	21824	65695;65696;65697	chr2:178548961;178548960;178548959	chr2:179413688;179413687;179413686
Novex-1	21949	66070;66071;66072	chr2:178548961;178548960;178548959	chr2:179413688;179413687;179413686
Novex-2	22016	66271;66272;66273	chr2:178548961;178548960;178548959	chr2:179413688;179413687;179413686
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-113
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.346
• 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
G/D	rs727505280	-0.992	0.991	N	0.807	0.453	0.408988072059	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	1.78E-05	0
G/D	rs727505280	-0.992	0.991	N	0.807	0.453	0.408988072059	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	4.77555E-04
G/D	rs727505280	-0.992	0.991	N	0.807	0.453	0.408988072059	gnomAD-4.0.0	5.20514E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.7806E-05	1.09784E-05	4.80292E-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
G/A	0.2098	likely_benign	0.209	benign	-0.503	Destabilizing	0.984	D	0.709	prob.delet.	N	0.490863208	None	None	N
G/C	0.322	likely_benign	0.3187	benign	-0.87	Destabilizing	1.0	D	0.86	deleterious	D	0.543747622	None	None	N
G/D	0.1815	likely_benign	0.1537	benign	-1.059	Destabilizing	0.991	D	0.807	deleterious	N	0.519660599	None	None	N
G/E	0.2491	likely_benign	0.2271	benign	-1.221	Destabilizing	0.997	D	0.871	deleterious	None	None	None	None	N
G/F	0.6784	likely_pathogenic	0.666	pathogenic	-1.17	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/H	0.4563	ambiguous	0.4364	ambiguous	-0.817	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
G/I	0.618	likely_pathogenic	0.6073	pathogenic	-0.565	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
G/K	0.5254	ambiguous	0.4917	ambiguous	-1.155	Destabilizing	0.993	D	0.877	deleterious	None	None	None	None	N
G/L	0.5185	ambiguous	0.5161	ambiguous	-0.565	Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
G/M	0.5403	ambiguous	0.5367	ambiguous	-0.475	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/N	0.179	likely_benign	0.1647	benign	-0.699	Destabilizing	0.379	N	0.66	neutral	None	None	None	None	N
G/P	0.9465	likely_pathogenic	0.9453	pathogenic	-0.51	Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
G/Q	0.3646	ambiguous	0.3455	ambiguous	-1.036	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
G/R	0.4084	ambiguous	0.3918	ambiguous	-0.613	Destabilizing	0.996	D	0.884	deleterious	N	0.504461239	None	None	N
G/S	0.111	likely_benign	0.1078	benign	-0.803	Destabilizing	0.991	D	0.785	deleterious	N	0.487709656	None	None	N
G/T	0.2597	likely_benign	0.2533	benign	-0.91	Destabilizing	0.997	D	0.857	deleterious	None	None	None	None	N
G/V	0.4558	ambiguous	0.4574	ambiguous	-0.51	Destabilizing	0.998	D	0.877	deleterious	N	0.520363448	None	None	N
G/W	0.5162	ambiguous	0.5333	ambiguous	-1.33	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/Y	0.5081	ambiguous	0.4973	ambiguous	-1.007	Destabilizing	1.0	D	0.865	deleterious	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.