TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31072	93439;93440;93441	chr2:178548412;178548411;178548410	chr2:179413139;179413138;179413137
N2AB	29431	88516;88517;88518	chr2:178548412;178548411;178548410	chr2:179413139;179413138;179413137
N2A	28504	85735;85736;85737	chr2:178548412;178548411;178548410	chr2:179413139;179413138;179413137
N2B	22007	66244;66245;66246	chr2:178548412;178548411;178548410	chr2:179413139;179413138;179413137
Novex-1	22132	66619;66620;66621	chr2:178548412;178548411;178548410	chr2:179413139;179413138;179413137
Novex-2	22199	66820;66821;66822	chr2:178548412;178548411;178548410	chr2:179413139;179413138;179413137
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: Fn3-114
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.7218
• 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
R/C	rs368932767	0.019	1.0	N	0.639	0.422	None	gnomAD-2.1.1	5.37E-05	None	None	None	None	N	None	4.14E-05	0	None	0	5.12E-05	None	0	None	7.99E-05	8.63E-05	0
R/C	rs368932767	0.019	1.0	N	0.639	0.422	None	gnomAD-3.1.2	1.05184E-04	None	None	None	None	N	None	7.24E-05	6.55E-05	0	0	0	None	9.42E-05	0	1.61727E-04	0	0
R/C	rs368932767	0.019	1.0	N	0.639	0.422	None	gnomAD-4.0.0	1.14644E-04	None	None	None	None	N	None	5.34017E-05	1.66711E-05	None	0	1.55971E-04	None	3.12529E-05	0	1.33921E-04	1.09796E-05	1.92111E-04
R/G	rs368932767	-0.154	0.998	N	0.475	0.413	0.451882325854	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/G	rs368932767	-0.154	0.998	N	0.475	0.413	0.451882325854	gnomAD-4.0.0	2.05257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47802E-05	0
R/H	rs141817409	-0.69	0.783	N	0.297	0.265	None	gnomAD-2.1.1	1.14448E-04	None	None	None	None	N	None	9.51199E-04	1.97997E-04	None	0	0	None	0	None	4E-05	7.84E-06	0
R/H	rs141817409	-0.69	0.783	N	0.297	0.265	None	gnomAD-3.1.2	2.8928E-04	None	None	None	None	N	None	9.41256E-04	6.55E-05	0	0	1.93125E-04	None	9.43E-05	0	2.94E-05	0	0
R/H	rs141817409	-0.69	0.783	N	0.297	0.265	None	1000 genomes	7.98722E-04	None	None	None	None	N	None	3E-03	0	None	None	0	0	None	None	None	0	None
R/H	rs141817409	-0.69	0.783	N	0.297	0.265	None	gnomAD-4.0.0	7.74568E-05	None	None	None	None	N	None	1.07957E-03	1.83284E-04	None	0	6.68688E-05	None	1.56299E-05	0	2.11902E-05	0	6.40184E-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	0.843	likely_pathogenic	0.8013	pathogenic	0.096	Stabilizing	0.996	D	0.536	neutral	None	None	None	None	N
R/C	0.4655	ambiguous	0.4595	ambiguous	-0.172	Destabilizing	1.0	D	0.639	neutral	N	0.482004301	None	None	N
R/D	0.9428	likely_pathogenic	0.9229	pathogenic	-0.214	Destabilizing	0.999	D	0.553	neutral	None	None	None	None	N
R/E	0.8349	likely_pathogenic	0.7849	pathogenic	-0.156	Destabilizing	0.992	D	0.522	neutral	None	None	None	None	N
R/F	0.9118	likely_pathogenic	0.8979	pathogenic	-0.161	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
R/G	0.6424	likely_pathogenic	0.5882	pathogenic	-0.077	Destabilizing	0.998	D	0.475	neutral	N	0.47442138	None	None	N
R/H	0.2595	likely_benign	0.2412	benign	-0.59	Destabilizing	0.783	D	0.297	neutral	N	0.520231028	None	None	N
R/I	0.8414	likely_pathogenic	0.7772	pathogenic	0.509	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
R/K	0.2485	likely_benign	0.2369	benign	-0.069	Destabilizing	0.99	D	0.496	neutral	None	None	None	None	N
R/L	0.6771	likely_pathogenic	0.6284	pathogenic	0.509	Stabilizing	0.999	D	0.477	neutral	N	0.470519411	None	None	N
R/M	0.798	likely_pathogenic	0.7469	pathogenic	0.004	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	N
R/N	0.9028	likely_pathogenic	0.881	pathogenic	0.034	Stabilizing	0.992	D	0.549	neutral	None	None	None	None	N
R/P	0.9393	likely_pathogenic	0.9212	pathogenic	0.391	Stabilizing	1.0	D	0.6	neutral	N	0.465746471	None	None	N
R/Q	0.2762	likely_benign	0.247	benign	-0.004	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
R/S	0.8633	likely_pathogenic	0.8255	pathogenic	-0.184	Destabilizing	0.998	D	0.54	neutral	N	0.460201289	None	None	N
R/T	0.7982	likely_pathogenic	0.7149	pathogenic	-0.004	Destabilizing	1.0	D	0.537	neutral	None	None	None	None	N
R/V	0.8537	likely_pathogenic	0.8072	pathogenic	0.391	Stabilizing	1.0	D	0.622	neutral	None	None	None	None	N
R/W	0.4744	ambiguous	0.4449	ambiguous	-0.306	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
R/Y	0.7363	likely_pathogenic	0.7216	pathogenic	0.111	Stabilizing	0.998	D	0.609	neutral	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.