TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32155	96688;96689;96690	chr2:178543510;178543509;178543508	chr2:179408237;179408236;179408235
N2AB	30514	91765;91766;91767	chr2:178543510;178543509;178543508	chr2:179408237;179408236;179408235
N2A	29587	88984;88985;88986	chr2:178543510;178543509;178543508	chr2:179408237;179408236;179408235
N2B	23090	69493;69494;69495	chr2:178543510;178543509;178543508	chr2:179408237;179408236;179408235
Novex-1	23215	69868;69869;69870	chr2:178543510;178543509;178543508	chr2:179408237;179408236;179408235
Novex-2	23282	70069;70070;70071	chr2:178543510;178543509;178543508	chr2:179408237;179408236;179408235
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-122
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2038
• 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
V/A	rs1442205432	None	0.858	N	0.474	0.308	0.50857664894	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
V/A	rs1442205432	None	0.858	N	0.474	0.308	0.50857664894	gnomAD-4.0.0	6.57212E-06	None	None	None	None	N	None	0	6.54879E-05	None	0	0	None	0	0	0	0	0
V/I	None	None	0.003	N	0.261	0.077	0.371344866733	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.368	ambiguous	0.317	benign	-1.454	Destabilizing	0.858	D	0.474	neutral	N	0.518596232	None	None	N
V/C	0.8515	likely_pathogenic	0.8489	pathogenic	-1.077	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
V/D	0.944	likely_pathogenic	0.9173	pathogenic	-1.136	Destabilizing	0.998	D	0.846	deleterious	None	None	None	None	N
V/E	0.8236	likely_pathogenic	0.775	pathogenic	-1.075	Destabilizing	0.981	D	0.8	deleterious	N	0.488396629	None	None	N
V/F	0.5201	ambiguous	0.4873	ambiguous	-1.026	Destabilizing	0.981	D	0.817	deleterious	None	None	None	None	N
V/G	0.7743	likely_pathogenic	0.6926	pathogenic	-1.827	Destabilizing	0.993	D	0.813	deleterious	N	0.492550913	None	None	N
V/H	0.9455	likely_pathogenic	0.9321	pathogenic	-1.312	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
V/I	0.0841	likely_benign	0.0802	benign	-0.511	Destabilizing	0.003	N	0.261	neutral	N	0.520057669	None	None	N
V/K	0.9233	likely_pathogenic	0.8999	pathogenic	-1.164	Destabilizing	0.98	D	0.807	deleterious	None	None	None	None	N
V/L	0.4011	ambiguous	0.3558	ambiguous	-0.511	Destabilizing	0.063	N	0.415	neutral	N	0.493583144	None	None	N
V/M	0.288	likely_benign	0.2441	benign	-0.484	Destabilizing	0.974	D	0.718	prob.delet.	None	None	None	None	N
V/N	0.8432	likely_pathogenic	0.7899	pathogenic	-1.14	Destabilizing	0.957	D	0.842	deleterious	None	None	None	None	N
V/P	0.9831	likely_pathogenic	0.9696	pathogenic	-0.79	Destabilizing	0.957	D	0.831	deleterious	None	None	None	None	N
V/Q	0.8295	likely_pathogenic	0.7872	pathogenic	-1.192	Destabilizing	0.991	D	0.831	deleterious	None	None	None	None	N
V/R	0.9064	likely_pathogenic	0.8776	pathogenic	-0.764	Destabilizing	0.997	D	0.843	deleterious	None	None	None	None	N
V/S	0.6353	likely_pathogenic	0.5626	ambiguous	-1.73	Destabilizing	0.983	D	0.789	deleterious	None	None	None	None	N
V/T	0.5111	ambiguous	0.4482	ambiguous	-1.536	Destabilizing	0.764	D	0.608	neutral	None	None	None	None	N
V/W	0.982	likely_pathogenic	0.9763	pathogenic	-1.27	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/Y	0.9094	likely_pathogenic	0.8921	pathogenic	-0.923	Destabilizing	0.991	D	0.825	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.