TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16639	50140;50141;50142	chr2:178612806;178612805;178612804	chr2:179477533;179477532;179477531
N2AB	14998	45217;45218;45219	chr2:178612806;178612805;178612804	chr2:179477533;179477532;179477531
N2A	14071	42436;42437;42438	chr2:178612806;178612805;178612804	chr2:179477533;179477532;179477531
N2B	7574	22945;22946;22947	chr2:178612806;178612805;178612804	chr2:179477533;179477532;179477531
Novex-1	7699	23320;23321;23322	chr2:178612806;178612805;178612804	chr2:179477533;179477532;179477531
Novex-2	7766	23521;23522;23523	chr2:178612806;178612805;178612804	chr2:179477533;179477532;179477531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-8
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.3217
• 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
P/T	None	None	0.972	N	0.814	0.278	0.33835085245	gnomAD-4.0.0	1.20037E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31256E-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
P/A	0.1014	likely_benign	0.1138	benign	-1.607	Destabilizing	0.908	D	0.726	deleterious	N	0.46955764	None	None	N
P/C	0.7934	likely_pathogenic	0.8068	pathogenic	-0.983	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/D	0.6835	likely_pathogenic	0.7604	pathogenic	-1.411	Destabilizing	0.989	D	0.743	deleterious	None	None	None	None	N
P/E	0.5128	ambiguous	0.5972	pathogenic	-1.408	Destabilizing	0.989	D	0.757	deleterious	None	None	None	None	N
P/F	0.7714	likely_pathogenic	0.8132	pathogenic	-1.327	Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	N
P/G	0.5847	likely_pathogenic	0.6349	pathogenic	-1.929	Destabilizing	0.929	D	0.821	deleterious	None	None	None	None	N
P/H	0.5087	ambiguous	0.5984	pathogenic	-1.471	Destabilizing	0.999	D	0.858	deleterious	N	0.519504288	None	None	N
P/I	0.4325	ambiguous	0.4881	ambiguous	-0.812	Destabilizing	0.995	D	0.887	deleterious	None	None	None	None	N
P/K	0.6466	likely_pathogenic	0.7533	pathogenic	-1.115	Destabilizing	0.989	D	0.735	deleterious	None	None	None	None	N
P/L	0.2531	likely_benign	0.2993	benign	-0.812	Destabilizing	0.986	D	0.825	deleterious	N	0.475376751	None	None	N
P/M	0.5448	ambiguous	0.5784	pathogenic	-0.58	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/N	0.6555	likely_pathogenic	0.7027	pathogenic	-0.898	Destabilizing	0.989	D	0.86	deleterious	None	None	None	None	N
P/Q	0.408	ambiguous	0.4885	ambiguous	-1.09	Destabilizing	0.995	D	0.794	deleterious	None	None	None	None	N
P/R	0.5026	ambiguous	0.6447	pathogenic	-0.617	Destabilizing	0.986	D	0.863	deleterious	D	0.543471611	None	None	N
P/S	0.2539	likely_benign	0.2954	benign	-1.444	Destabilizing	0.379	N	0.371	neutral	N	0.475619714	None	None	N
P/T	0.2165	likely_benign	0.2641	benign	-1.331	Destabilizing	0.972	D	0.814	deleterious	N	0.472740015	None	None	N
P/V	0.3065	likely_benign	0.3557	ambiguous	-1.043	Destabilizing	0.989	D	0.834	deleterious	None	None	None	None	N
P/W	0.9094	likely_pathogenic	0.9369	pathogenic	-1.51	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/Y	0.7527	likely_pathogenic	0.8049	pathogenic	-1.212	Destabilizing	1.0	D	0.897	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.