TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32072	96439;96440;96441	chr2:178543930;178543929;178543928	chr2:179408657;179408656;179408655
N2AB	30431	91516;91517;91518	chr2:178543930;178543929;178543928	chr2:179408657;179408656;179408655
N2A	29504	88735;88736;88737	chr2:178543930;178543929;178543928	chr2:179408657;179408656;179408655
N2B	23007	69244;69245;69246	chr2:178543930;178543929;178543928	chr2:179408657;179408656;179408655
Novex-1	23132	69619;69620;69621	chr2:178543930;178543929;178543928	chr2:179408657;179408656;179408655
Novex-2	23199	69820;69821;69822	chr2:178543930;178543929;178543928	chr2:179408657;179408656;179408655
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-153
• Domain position: 56
• Structural Position: 140
• Q(SASA): 0.1801
• 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/G	None	None	0.971	D	0.87	0.696	0.932966899989	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
V/L	rs1375176606	-0.612	0.247	N	0.523	0.237	0.365317461125	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/L	rs1375176606	-0.612	0.247	N	0.523	0.237	0.365317461125	gnomAD-4.0.0	1.59139E-06	None	None	None	None	N	None	5.65867E-05	0	None	0	0	None	0	0	0	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	0.5686	likely_pathogenic	0.4873	ambiguous	-2.212	Highly Destabilizing	0.822	D	0.678	prob.neutral	D	0.524880715	None	None	N
V/C	0.8936	likely_pathogenic	0.8764	pathogenic	-1.926	Destabilizing	0.998	D	0.75	deleterious	None	None	None	None	N
V/D	0.9787	likely_pathogenic	0.9684	pathogenic	-2.887	Highly Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
V/E	0.9498	likely_pathogenic	0.9283	pathogenic	-2.74	Highly Destabilizing	0.99	D	0.86	deleterious	N	0.514284878	None	None	N
V/F	0.6205	likely_pathogenic	0.5513	ambiguous	-1.452	Destabilizing	0.956	D	0.768	deleterious	None	None	None	None	N
V/G	0.8627	likely_pathogenic	0.8157	pathogenic	-2.685	Highly Destabilizing	0.971	D	0.87	deleterious	D	0.525641184	None	None	N
V/H	0.98	likely_pathogenic	0.971	pathogenic	-2.336	Highly Destabilizing	0.998	D	0.844	deleterious	None	None	None	None	N
V/I	0.075	likely_benign	0.0733	benign	-0.924	Destabilizing	0.019	N	0.338	neutral	None	None	None	None	N
V/K	0.9673	likely_pathogenic	0.9515	pathogenic	-2.054	Highly Destabilizing	0.978	D	0.866	deleterious	None	None	None	None	N
V/L	0.3166	likely_benign	0.2815	benign	-0.924	Destabilizing	0.247	N	0.523	neutral	N	0.447478	None	None	N
V/M	0.3053	likely_benign	0.2632	benign	-0.933	Destabilizing	0.489	N	0.575	neutral	N	0.489379767	None	None	N
V/N	0.9371	likely_pathogenic	0.9141	pathogenic	-2.237	Highly Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
V/P	0.9879	likely_pathogenic	0.9822	pathogenic	-1.324	Destabilizing	0.993	D	0.858	deleterious	None	None	None	None	N
V/Q	0.948	likely_pathogenic	0.9247	pathogenic	-2.21	Highly Destabilizing	0.978	D	0.854	deleterious	None	None	None	None	N
V/R	0.9545	likely_pathogenic	0.9297	pathogenic	-1.65	Destabilizing	0.978	D	0.863	deleterious	None	None	None	None	N
V/S	0.8056	likely_pathogenic	0.751	pathogenic	-2.81	Highly Destabilizing	0.978	D	0.844	deleterious	None	None	None	None	N
V/T	0.5623	ambiguous	0.4859	ambiguous	-2.536	Highly Destabilizing	0.86	D	0.703	prob.neutral	None	None	None	None	N
V/W	0.9872	likely_pathogenic	0.9795	pathogenic	-1.899	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
V/Y	0.9552	likely_pathogenic	0.9356	pathogenic	-1.575	Destabilizing	0.978	D	0.763	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.