TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25537	76834;76835;76836	chr2:178569523;178569522;178569521	chr2:179434250;179434249;179434248
N2AB	23896	71911;71912;71913	chr2:178569523;178569522;178569521	chr2:179434250;179434249;179434248
N2A	22969	69130;69131;69132	chr2:178569523;178569522;178569521	chr2:179434250;179434249;179434248
N2B	16472	49639;49640;49641	chr2:178569523;178569522;178569521	chr2:179434250;179434249;179434248
Novex-1	16597	50014;50015;50016	chr2:178569523;178569522;178569521	chr2:179434250;179434249;179434248
Novex-2	16664	50215;50216;50217	chr2:178569523;178569522;178569521	chr2:179434250;179434249;179434248
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Ig-135
• Domain position: 24
• Structural Position: 41
• Q(SASA): 0.7785
• Predicted PPI site: I

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
R/C	rs527631472	-0.196	1.0	N	0.67	0.474	0.608244025668	gnomAD-2.1.1	8.07E-06	None	None	None	None	I	None	0	0	None	0	5.61E-05	None	0	None	0	8.91E-06	0
R/C	rs527631472	-0.196	1.0	N	0.67	0.474	0.608244025668	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
R/C	rs527631472	-0.196	1.0	N	0.67	0.474	0.608244025668	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	1E-03	None	None	None	0	None
R/C	rs527631472	-0.196	1.0	N	0.67	0.474	0.608244025668	gnomAD-4.0.0	3.10092E-06	None	None	None	None	I	None	0	0	None	0	2.23594E-05	None	0	0	2.54424E-06	1.09965E-05	0
R/G	rs527631472	-0.288	0.998	D	0.583	0.468	0.613844073566	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
R/G	rs527631472	-0.288	0.998	D	0.583	0.468	0.613844073566	gnomAD-4.0.0	2.05425E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	3.48303E-05	0
R/H	rs561977468	-0.542	0.783	D	0.425	0.318	None	gnomAD-2.1.1	1.397E-04	None	None	None	None	I	None	1.65412E-04	0	None	0	1.60074E-03	None	0	None	0	2.35E-05	1.41283E-04
R/H	rs561977468	-0.542	0.783	D	0.425	0.318	None	gnomAD-3.1.2	8.55E-05	None	None	None	None	I	None	1.20703E-04	0	0	0	9.67867E-04	None	0	0	4.41E-05	0	0
R/H	rs561977468	-0.542	0.783	D	0.425	0.318	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/H	rs561977468	-0.542	0.783	D	0.425	0.318	None	gnomAD-4.0.0	4.65074E-05	None	None	None	None	I	None	1.20131E-04	1.66939E-05	None	0	6.25978E-04	None	0	1.65344E-04	2.28965E-05	4.39754E-05	8.01E-05

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
R/A	0.9567	likely_pathogenic	0.9606	pathogenic	0.071	Stabilizing	0.996	D	0.635	neutral	None	None	None	None	I
R/C	0.4251	ambiguous	0.4322	ambiguous	-0.092	Destabilizing	1.0	D	0.67	neutral	N	0.506127669	None	None	I
R/D	0.9875	likely_pathogenic	0.9887	pathogenic	-0.213	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	I
R/E	0.9135	likely_pathogenic	0.9238	pathogenic	-0.162	Destabilizing	0.992	D	0.603	neutral	None	None	None	None	I
R/F	0.8532	likely_pathogenic	0.863	pathogenic	-0.179	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
R/G	0.9404	likely_pathogenic	0.9455	pathogenic	-0.099	Destabilizing	0.998	D	0.583	neutral	D	0.528586791	None	None	I
R/H	0.2308	likely_benign	0.235	benign	-0.61	Destabilizing	0.783	D	0.425	neutral	D	0.531211318	None	None	I
R/I	0.6546	likely_pathogenic	0.6929	pathogenic	0.479	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	I
R/K	0.2173	likely_benign	0.2244	benign	-0.047	Destabilizing	0.99	D	0.539	neutral	None	None	None	None	I
R/L	0.7306	likely_pathogenic	0.7423	pathogenic	0.479	Stabilizing	0.999	D	0.568	neutral	D	0.530864601	None	None	I
R/M	0.7804	likely_pathogenic	0.7892	pathogenic	0.04	Stabilizing	1.0	D	0.59	neutral	None	None	None	None	I
R/N	0.9363	likely_pathogenic	0.9448	pathogenic	0.14	Stabilizing	0.992	D	0.592	neutral	None	None	None	None	I
R/P	0.997	likely_pathogenic	0.997	pathogenic	0.362	Stabilizing	1.0	D	0.611	neutral	D	0.52884028	None	None	I
R/Q	0.3055	likely_benign	0.3174	benign	0.065	Stabilizing	0.999	D	0.582	neutral	None	None	None	None	I
R/S	0.9491	likely_pathogenic	0.954	pathogenic	-0.099	Destabilizing	0.998	D	0.613	neutral	D	0.522647762	None	None	I
R/T	0.8833	likely_pathogenic	0.9012	pathogenic	0.071	Stabilizing	1.0	D	0.575	neutral	None	None	None	None	I
R/V	0.7936	likely_pathogenic	0.8167	pathogenic	0.362	Stabilizing	1.0	D	0.618	neutral	None	None	None	None	I
R/W	0.4497	ambiguous	0.4626	ambiguous	-0.305	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
R/Y	0.655	likely_pathogenic	0.6803	pathogenic	0.102	Stabilizing	0.998	D	0.605	neutral	None	None	None	None	I

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.