TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20899	62920;62921;62922	chr2:178589030;178589029;178589028	chr2:179453757;179453756;179453755
N2AB	19258	57997;57998;57999	chr2:178589030;178589029;178589028	chr2:179453757;179453756;179453755
N2A	18331	55216;55217;55218	chr2:178589030;178589029;178589028	chr2:179453757;179453756;179453755
N2B	11834	35725;35726;35727	chr2:178589030;178589029;178589028	chr2:179453757;179453756;179453755
Novex-1	11959	36100;36101;36102	chr2:178589030;178589029;178589028	chr2:179453757;179453756;179453755
Novex-2	12026	36301;36302;36303	chr2:178589030;178589029;178589028	chr2:179453757;179453756;179453755
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-39
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1088
• 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
Y/C	rs564111693	-1.807	1.0	D	0.877	0.815	0.890340196367	gnomAD-2.1.1	8.16E-06	None	None	None	None	N	None	0	5.83E-05	None	0	0	None	0	None	0	0	0
Y/C	rs564111693	-1.807	1.0	D	0.877	0.815	0.890340196367	gnomAD-4.0.0	8.00228E-06	None	None	None	None	N	None	0	6.87348E-05	None	0	0	None	0	0	5.72099E-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
Y/A	0.9965	likely_pathogenic	0.9956	pathogenic	-3.525	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/C	0.9168	likely_pathogenic	0.9117	pathogenic	-1.973	Destabilizing	1.0	D	0.877	deleterious	D	0.642118767	None	None	N
Y/D	0.9968	likely_pathogenic	0.996	pathogenic	-3.85	Highly Destabilizing	1.0	D	0.908	deleterious	D	0.642522375	None	None	N
Y/E	0.9993	likely_pathogenic	0.9991	pathogenic	-3.627	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
Y/F	0.2184	likely_benign	0.2159	benign	-1.375	Destabilizing	0.999	D	0.649	neutral	D	0.561296903	None	None	N
Y/G	0.9923	likely_pathogenic	0.9905	pathogenic	-3.941	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/H	0.9668	likely_pathogenic	0.96	pathogenic	-2.648	Highly Destabilizing	1.0	D	0.796	deleterious	D	0.642118767	None	None	N
Y/I	0.9747	likely_pathogenic	0.9706	pathogenic	-2.112	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/K	0.9988	likely_pathogenic	0.9986	pathogenic	-2.458	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/L	0.952	likely_pathogenic	0.9446	pathogenic	-2.112	Highly Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
Y/M	0.9846	likely_pathogenic	0.9824	pathogenic	-1.863	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
Y/N	0.9774	likely_pathogenic	0.9728	pathogenic	-3.273	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.642522375	None	None	N
Y/P	0.9995	likely_pathogenic	0.9994	pathogenic	-2.604	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
Y/Q	0.9982	likely_pathogenic	0.9976	pathogenic	-2.993	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/R	0.9937	likely_pathogenic	0.9929	pathogenic	-2.258	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/S	0.988	likely_pathogenic	0.9844	pathogenic	-3.586	Highly Destabilizing	1.0	D	0.904	deleterious	D	0.642522375	None	None	N
Y/T	0.995	likely_pathogenic	0.9935	pathogenic	-3.24	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
Y/V	0.953	likely_pathogenic	0.946	pathogenic	-2.604	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
Y/W	0.8493	likely_pathogenic	0.8501	pathogenic	-0.581	Destabilizing	1.0	D	0.787	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.