TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27607	83044;83045;83046	chr2:178563313;178563312;178563311	chr2:179428040;179428039;179428038
N2AB	25966	78121;78122;78123	chr2:178563313;178563312;178563311	chr2:179428040;179428039;179428038
N2A	25039	75340;75341;75342	chr2:178563313;178563312;178563311	chr2:179428040;179428039;179428038
N2B	18542	55849;55850;55851	chr2:178563313;178563312;178563311	chr2:179428040;179428039;179428038
Novex-1	18667	56224;56225;56226	chr2:178563313;178563312;178563311	chr2:179428040;179428039;179428038
Novex-2	18734	56425;56426;56427	chr2:178563313;178563312;178563311	chr2:179428040;179428039;179428038
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: Fn3-89
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0711
• 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	rs752494467	-2.548	0.334	D	0.613	0.517	0.662910326475	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/A	rs752494467	-2.548	0.334	D	0.613	0.517	0.662910326475	gnomAD-4.0.0	2.05281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69855E-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	0.7034	likely_pathogenic	0.6786	pathogenic	-2.197	Highly Destabilizing	0.334	N	0.613	neutral	D	0.532095964	None	None	N
V/C	0.9634	likely_pathogenic	0.9665	pathogenic	-1.777	Destabilizing	0.982	D	0.797	deleterious	None	None	None	None	N
V/D	0.9981	likely_pathogenic	0.9977	pathogenic	-3.359	Highly Destabilizing	0.826	D	0.873	deleterious	None	None	None	None	N
V/E	0.9924	likely_pathogenic	0.9912	pathogenic	-3.029	Highly Destabilizing	0.781	D	0.863	deleterious	D	0.562316993	None	None	N
V/F	0.8529	likely_pathogenic	0.8697	pathogenic	-1.237	Destabilizing	0.7	D	0.805	deleterious	None	None	None	None	N
V/G	0.9406	likely_pathogenic	0.931	pathogenic	-2.823	Highly Destabilizing	0.781	D	0.875	deleterious	D	0.562316993	None	None	N
V/H	0.9981	likely_pathogenic	0.9982	pathogenic	-2.841	Highly Destabilizing	0.982	D	0.873	deleterious	None	None	None	None	N
V/I	0.0792	likely_benign	0.0875	benign	-0.374	Destabilizing	0.002	N	0.269	neutral	N	0.491164488	None	None	N
V/K	0.9948	likely_pathogenic	0.9941	pathogenic	-1.859	Destabilizing	0.826	D	0.863	deleterious	None	None	None	None	N
V/L	0.3786	ambiguous	0.3815	ambiguous	-0.374	Destabilizing	0.034	N	0.523	neutral	N	0.50421393	None	None	N
V/M	0.5642	likely_pathogenic	0.5785	pathogenic	-0.69	Destabilizing	0.7	D	0.699	prob.neutral	None	None	None	None	N
V/N	0.9941	likely_pathogenic	0.9939	pathogenic	-2.586	Highly Destabilizing	0.935	D	0.883	deleterious	None	None	None	None	N
V/P	0.9894	likely_pathogenic	0.9892	pathogenic	-0.963	Destabilizing	0.935	D	0.868	deleterious	None	None	None	None	N
V/Q	0.992	likely_pathogenic	0.9914	pathogenic	-2.202	Highly Destabilizing	0.935	D	0.883	deleterious	None	None	None	None	N
V/R	0.9892	likely_pathogenic	0.988	pathogenic	-2.039	Highly Destabilizing	0.826	D	0.885	deleterious	None	None	None	None	N
V/S	0.9613	likely_pathogenic	0.9584	pathogenic	-3.081	Highly Destabilizing	0.826	D	0.865	deleterious	None	None	None	None	N
V/T	0.8129	likely_pathogenic	0.7991	pathogenic	-2.582	Highly Destabilizing	0.399	N	0.67	neutral	None	None	None	None	N
V/W	0.9966	likely_pathogenic	0.9973	pathogenic	-1.857	Destabilizing	0.982	D	0.847	deleterious	None	None	None	None	N
V/Y	0.9901	likely_pathogenic	0.9911	pathogenic	-1.492	Destabilizing	0.826	D	0.806	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.