TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14996	45211;45212;45213	chr2:178621936;178621935;178621934	chr2:179486663;179486662;179486661
N2AB	13355	40288;40289;40290	chr2:178621936;178621935;178621934	chr2:179486663;179486662;179486661
N2A	12428	37507;37508;37509	chr2:178621936;178621935;178621934	chr2:179486663;179486662;179486661
N2B	5931	18016;18017;18018	chr2:178621936;178621935;178621934	chr2:179486663;179486662;179486661
Novex-1	6056	18391;18392;18393	chr2:178621936;178621935;178621934	chr2:179486663;179486662;179486661
Novex-2	6123	18592;18593;18594	chr2:178621936;178621935;178621934	chr2:179486663;179486662;179486661
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-101
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1009
• 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	rs765602798	-2.079	0.999	N	0.789	0.309	0.247872288689	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	8.92E-06	0
R/C	rs765602798	-2.079	0.999	N	0.789	0.309	0.247872288689	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/C	rs765602798	-2.079	0.999	N	0.789	0.309	0.247872288689	gnomAD-4.0.0	1.24086E-05	None	None	None	None	N	None	0	1.67319E-05	None	0	2.24487E-05	None	0	0	1.35722E-05	2.19785E-05	0
R/H	rs762128685	-2.393	0.029	N	0.433	0.15	None	gnomAD-2.1.1	2.43E-05	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	4.46E-05	0
R/H	rs762128685	-2.393	0.029	N	0.433	0.15	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	2.94E-05	0	0
R/H	rs762128685	-2.393	0.029	N	0.433	0.15	None	gnomAD-4.0.0	5.70811E-05	None	None	None	None	N	None	2.67308E-05	3.34717E-05	None	0	0	None	0	1.64799E-04	7.21027E-05	0	3.20821E-05
R/L	rs762128685	-0.936	0.911	N	0.726	0.262	0.244539031024	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
R/L	rs762128685	-0.936	0.911	N	0.726	0.262	0.244539031024	gnomAD-4.0.0	4.11012E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.40081E-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
R/A	0.7536	likely_pathogenic	0.6969	pathogenic	-1.928	Destabilizing	0.842	D	0.72	prob.delet.	None	None	None	None	N
R/C	0.3051	likely_benign	0.2585	benign	-2.07	Highly Destabilizing	0.999	D	0.789	deleterious	N	0.437250542	None	None	N
R/D	0.9255	likely_pathogenic	0.9028	pathogenic	-1.19	Destabilizing	0.842	D	0.743	deleterious	None	None	None	None	N
R/E	0.7152	likely_pathogenic	0.6621	pathogenic	-0.982	Destabilizing	0.842	D	0.681	prob.neutral	None	None	None	None	N
R/F	0.8641	likely_pathogenic	0.8158	pathogenic	-1.329	Destabilizing	0.974	D	0.798	deleterious	None	None	None	None	N
R/G	0.6552	likely_pathogenic	0.587	pathogenic	-2.258	Highly Destabilizing	0.911	D	0.729	prob.delet.	D	0.595041179	None	None	N
R/H	0.1685	likely_benign	0.1456	benign	-2.233	Highly Destabilizing	0.029	N	0.433	neutral	N	0.447005898	None	None	N
R/I	0.6723	likely_pathogenic	0.5808	pathogenic	-0.977	Destabilizing	0.974	D	0.799	deleterious	None	None	None	None	N
R/K	0.2583	likely_benign	0.2422	benign	-1.507	Destabilizing	0.688	D	0.655	neutral	None	None	None	None	N
R/L	0.6057	likely_pathogenic	0.5347	ambiguous	-0.977	Destabilizing	0.911	D	0.726	prob.delet.	N	0.506325868	None	None	N
R/M	0.6681	likely_pathogenic	0.6025	pathogenic	-1.483	Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	N
R/N	0.7964	likely_pathogenic	0.7702	pathogenic	-1.515	Destabilizing	0.842	D	0.693	prob.neutral	None	None	None	None	N
R/P	0.9713	likely_pathogenic	0.9586	pathogenic	-1.282	Destabilizing	0.996	D	0.765	deleterious	D	0.600293922	None	None	N
R/Q	0.1738	likely_benign	0.1553	benign	-1.358	Destabilizing	0.842	D	0.711	prob.delet.	None	None	None	None	N
R/S	0.7639	likely_pathogenic	0.7127	pathogenic	-2.325	Highly Destabilizing	0.911	D	0.725	prob.delet.	N	0.43366414	None	None	N
R/T	0.5819	likely_pathogenic	0.4992	ambiguous	-1.906	Destabilizing	0.915	D	0.732	prob.delet.	None	None	None	None	N
R/V	0.7092	likely_pathogenic	0.6245	pathogenic	-1.282	Destabilizing	0.974	D	0.773	deleterious	None	None	None	None	N
R/W	0.404	ambiguous	0.3363	benign	-0.94	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
R/Y	0.6365	likely_pathogenic	0.5905	pathogenic	-0.727	Destabilizing	0.949	D	0.754	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.