TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25928	78007;78008;78009	chr2:178568350;178568349;178568348	chr2:179433077;179433076;179433075
N2AB	24287	73084;73085;73086	chr2:178568350;178568349;178568348	chr2:179433077;179433076;179433075
N2A	23360	70303;70304;70305	chr2:178568350;178568349;178568348	chr2:179433077;179433076;179433075
N2B	16863	50812;50813;50814	chr2:178568350;178568349;178568348	chr2:179433077;179433076;179433075
Novex-1	16988	51187;51188;51189	chr2:178568350;178568349;178568348	chr2:179433077;179433076;179433075
Novex-2	17055	51388;51389;51390	chr2:178568350;178568349;178568348	chr2:179433077;179433076;179433075
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-76
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0766
• 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/I	None	None	0.067	N	0.303	0.121	0.388653054685	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.9092	likely_pathogenic	0.9415	pathogenic	-2.462	Highly Destabilizing	0.958	D	0.622	neutral	D	0.539831418	None	None	N
V/C	0.9692	likely_pathogenic	0.9771	pathogenic	-1.848	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/D	0.9994	likely_pathogenic	0.9997	pathogenic	-3.438	Highly Destabilizing	0.998	D	0.889	deleterious	D	0.563304498	None	None	N
V/E	0.9976	likely_pathogenic	0.9984	pathogenic	-3.097	Highly Destabilizing	0.998	D	0.876	deleterious	None	None	None	None	N
V/F	0.9012	likely_pathogenic	0.9377	pathogenic	-1.438	Destabilizing	0.988	D	0.839	deleterious	D	0.563051008	None	None	N
V/G	0.977	likely_pathogenic	0.9841	pathogenic	-3.099	Highly Destabilizing	0.994	D	0.885	deleterious	D	0.563304498	None	None	N
V/H	0.999	likely_pathogenic	0.9994	pathogenic	-3.014	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/I	0.0757	likely_benign	0.0808	benign	-0.598	Destabilizing	0.067	N	0.303	neutral	N	0.484699876	None	None	N
V/K	0.998	likely_pathogenic	0.9987	pathogenic	-2.134	Highly Destabilizing	0.995	D	0.877	deleterious	None	None	None	None	N
V/L	0.4046	ambiguous	0.4759	ambiguous	-0.598	Destabilizing	0.618	D	0.572	neutral	N	0.487726564	None	None	N
V/M	0.7387	likely_pathogenic	0.8124	pathogenic	-0.793	Destabilizing	0.991	D	0.759	deleterious	None	None	None	None	N
V/N	0.9976	likely_pathogenic	0.9987	pathogenic	-2.897	Highly Destabilizing	0.998	D	0.898	deleterious	None	None	None	None	N
V/P	0.9974	likely_pathogenic	0.9984	pathogenic	-1.201	Destabilizing	0.998	D	0.887	deleterious	None	None	None	None	N
V/Q	0.9964	likely_pathogenic	0.9976	pathogenic	-2.486	Highly Destabilizing	0.998	D	0.907	deleterious	None	None	None	None	N
V/R	0.9956	likely_pathogenic	0.9969	pathogenic	-2.267	Highly Destabilizing	0.998	D	0.904	deleterious	None	None	None	None	N
V/S	0.9867	likely_pathogenic	0.9919	pathogenic	-3.406	Highly Destabilizing	0.995	D	0.879	deleterious	None	None	None	None	N
V/T	0.9449	likely_pathogenic	0.9631	pathogenic	-2.894	Highly Destabilizing	0.968	D	0.689	prob.neutral	None	None	None	None	N
V/W	0.999	likely_pathogenic	0.9994	pathogenic	-2.004	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/Y	0.9948	likely_pathogenic	0.997	pathogenic	-1.683	Destabilizing	0.995	D	0.842	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.