TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18267	55024;55025;55026	chr2:178603888;178603887;178603886	chr2:179468615;179468614;179468613
N2AB	16626	50101;50102;50103	chr2:178603888;178603887;178603886	chr2:179468615;179468614;179468613
N2A	15699	47320;47321;47322	chr2:178603888;178603887;178603886	chr2:179468615;179468614;179468613
N2B	9202	27829;27830;27831	chr2:178603888;178603887;178603886	chr2:179468615;179468614;179468613
Novex-1	9327	28204;28205;28206	chr2:178603888;178603887;178603886	chr2:179468615;179468614;179468613
Novex-2	9394	28405;28406;28407	chr2:178603888;178603887;178603886	chr2:179468615;179468614;179468613
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-20
• Domain position: 102
• Structural Position: 131
• Q(SASA): 0.2485
• 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/E	rs878876923	None	0.013	N	0.541	0.166	0.275641507738	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/E	rs878876923	None	0.013	N	0.541	0.166	0.275641507738	gnomAD-4.0.0	2.61866E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.92858E-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
G/A	0.0733	likely_benign	0.0565	benign	-0.825	Destabilizing	None	N	0.091	neutral	N	0.458134924	None	None	N
G/C	0.1151	likely_benign	0.0999	benign	-1.091	Destabilizing	0.492	N	0.667	prob.neutral	None	None	None	None	N
G/D	0.2386	likely_benign	0.1589	benign	-1.903	Destabilizing	None	N	0.313	neutral	None	None	None	None	N
G/E	0.1467	likely_benign	0.0979	benign	-2.013	Highly Destabilizing	0.013	N	0.541	neutral	N	0.425675789	None	None	N
G/F	0.4512	ambiguous	0.2986	benign	-1.42	Destabilizing	0.204	N	0.733	deleterious	None	None	None	None	N
G/H	0.3064	likely_benign	0.2011	benign	-1.202	Destabilizing	0.492	N	0.61	neutral	None	None	None	None	N
G/I	0.1476	likely_benign	0.1007	benign	-0.687	Destabilizing	0.018	N	0.658	prob.neutral	None	None	None	None	N
G/K	0.2	likely_benign	0.1369	benign	-1.303	Destabilizing	0.018	N	0.596	neutral	None	None	None	None	N
G/L	0.2253	likely_benign	0.1426	benign	-0.687	Destabilizing	0.007	N	0.534	neutral	None	None	None	None	N
G/M	0.2597	likely_benign	0.1816	benign	-0.46	Destabilizing	0.204	N	0.677	prob.neutral	None	None	None	None	N
G/N	0.2768	likely_benign	0.1961	benign	-1.038	Destabilizing	0.018	N	0.567	neutral	None	None	None	None	N
G/P	0.9385	likely_pathogenic	0.8711	pathogenic	-0.698	Destabilizing	0.112	N	0.703	prob.delet.	None	None	None	None	N
G/Q	0.194	likely_benign	0.1304	benign	-1.38	Destabilizing	0.112	N	0.675	prob.neutral	None	None	None	None	N
G/R	0.1583	likely_benign	0.1061	benign	-0.814	Destabilizing	0.087	N	0.687	prob.delet.	N	0.402281641	None	None	N
G/S	0.0837	likely_benign	0.0694	benign	-1.141	Destabilizing	None	N	0.151	neutral	None	None	None	None	N
G/T	0.0832	likely_benign	0.0683	benign	-1.203	Destabilizing	0.007	N	0.537	neutral	None	None	None	None	N
G/V	0.0987	likely_benign	0.0729	benign	-0.698	Destabilizing	None	N	0.281	neutral	N	0.480915783	None	None	N
G/W	0.3792	ambiguous	0.2506	benign	-1.645	Destabilizing	0.747	D	0.647	neutral	None	None	None	None	N
G/Y	0.3897	ambiguous	0.2501	benign	-1.293	Destabilizing	0.204	N	0.729	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.