TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2990	9193;9194;9195	chr2:178768868;178768867;178768866	chr2:179633595;179633594;179633593
N2AB	2990	9193;9194;9195	chr2:178768868;178768867;178768866	chr2:179633595;179633594;179633593
N2A	2990	9193;9194;9195	chr2:178768868;178768867;178768866	chr2:179633595;179633594;179633593
N2B	2944	9055;9056;9057	chr2:178768868;178768867;178768866	chr2:179633595;179633594;179633593
Novex-1	2944	9055;9056;9057	chr2:178768868;178768867;178768866	chr2:179633595;179633594;179633593
Novex-2	2944	9055;9056;9057	chr2:178768868;178768867;178768866	chr2:179633595;179633594;179633593
Novex-3	2990	9193;9194;9195	chr2:178768868;178768867;178768866	chr2:179633595;179633594;179633593

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-20
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0759
• 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/M	rs746946974	-0.861	1.0	D	0.805	0.269	0.324161360171	gnomAD-2.1.1	2.39E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.4E-05	1.63132E-04
V/M	rs746946974	-0.861	1.0	D	0.805	0.269	0.324161360171	gnomAD-4.0.0	3.42052E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49652E-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	0.7859	likely_pathogenic	0.7858	pathogenic	-2.122	Highly Destabilizing	0.999	D	0.679	prob.neutral	N	0.452660053	None	None	N
V/C	0.9201	likely_pathogenic	0.9243	pathogenic	-1.997	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/D	0.9964	likely_pathogenic	0.9973	pathogenic	-3.049	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/E	0.9931	likely_pathogenic	0.994	pathogenic	-2.781	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.536396429	None	None	N
V/F	0.9745	likely_pathogenic	0.9675	pathogenic	-1.22	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/G	0.8672	likely_pathogenic	0.8787	pathogenic	-2.707	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.536210513	None	None	N
V/H	0.9989	likely_pathogenic	0.999	pathogenic	-2.595	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
V/I	0.2529	likely_benign	0.1998	benign	-0.457	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	N
V/K	0.9969	likely_pathogenic	0.9973	pathogenic	-1.707	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/L	0.9067	likely_pathogenic	0.8526	pathogenic	-0.457	Destabilizing	0.997	D	0.677	prob.neutral	N	0.457870117	None	None	N
V/M	0.841	likely_pathogenic	0.8207	pathogenic	-0.815	Destabilizing	1.0	D	0.805	deleterious	D	0.536210513	None	None	N
V/N	0.9848	likely_pathogenic	0.9878	pathogenic	-2.226	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
V/P	0.9993	likely_pathogenic	0.999	pathogenic	-0.988	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/Q	0.9955	likely_pathogenic	0.9961	pathogenic	-1.971	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/R	0.9961	likely_pathogenic	0.996	pathogenic	-1.702	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
V/S	0.9299	likely_pathogenic	0.9493	pathogenic	-2.822	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/T	0.7872	likely_pathogenic	0.8287	pathogenic	-2.395	Highly Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.806	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/Y	0.9968	likely_pathogenic	0.9964	pathogenic	-1.423	Destabilizing	1.0	D	0.835	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.