TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17699	53320;53321;53322	chr2:178607593;178607592;178607591	chr2:179472320;179472319;179472318
N2AB	16058	48397;48398;48399	chr2:178607593;178607592;178607591	chr2:179472320;179472319;179472318
N2A	15131	45616;45617;45618	chr2:178607593;178607592;178607591	chr2:179472320;179472319;179472318
N2B	8634	26125;26126;26127	chr2:178607593;178607592;178607591	chr2:179472320;179472319;179472318
Novex-1	8759	26500;26501;26502	chr2:178607593;178607592;178607591	chr2:179472320;179472319;179472318
Novex-2	8826	26701;26702;26703	chr2:178607593;178607592;178607591	chr2:179472320;179472319;179472318
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-113
• Domain position: 23
• Structural Position: 41
• Q(SASA): 0.5384
• 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	rs760963888	-0.043	1.0	N	0.651	0.412	0.612736520223	gnomAD-2.1.1	2.51E-05	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	3.15E-05	1.40568E-04
R/C	rs760963888	-0.043	1.0	N	0.651	0.412	0.612736520223	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.95E-05	0	0
R/C	rs760963888	-0.043	1.0	N	0.651	0.412	0.612736520223	gnomAD-4.0.0	1.48798E-05	None	None	None	None	I	None	0	6.67178E-05	None	0	0	None	0	0	1.18708E-05	6.58848E-05	0
R/H	None	-0.609	1.0	N	0.501	0.365	None	gnomAD-2.1.1	1.77036E-03	None	None	None	None	I	None	6.62691E-04	1.07527E-03	None	1.35633E-03	7.19868E-04	None	1.69957E-03	None	1.60013E-04	2.73852E-03	1.12423E-03
R/H	None	-0.609	1.0	N	0.501	0.365	None	gnomAD-3.1.2	1.58636E-03	None	None	None	None	I	None	6.76459E-04	1.37777E-03	0	1.15274E-03	5.8434E-04	None	2.82805E-04	0	2.57626E-03	1.03605E-03	9.56023E-04
R/H	None	-0.609	1.0	N	0.501	0.365	None	1000 genomes	1.19808E-03	None	None	None	None	I	None	8E-04	1.4E-03	None	None	0	3E-03	None	None	None	1E-03	None
R/H	None	-0.609	1.0	N	0.501	0.365	None	gnomAD-4.0.0	2.24162E-03	None	None	None	None	I	None	5.60403E-04	1.20052E-03	None	1.01372E-03	4.24202E-04	None	5.1598E-04	4.9554E-04	2.67599E-03	1.72395E-03	1.66549E-03
R/L	rs72646808	0.511	0.996	N	0.565	0.368	0.54988173901	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
R/L	rs72646808	0.511	0.996	N	0.565	0.368	0.54988173901	gnomAD-4.0.0	1.36885E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79944E-06	0	0
R/P	rs72646808	None	1.0	N	0.585	0.415	0.608695890411	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
R/P	rs72646808	None	1.0	N	0.585	0.415	0.608695890411	gnomAD-4.0.0	1.85989E-06	None	None	None	None	I	None	4.00941E-05	0	None	0	0	None	0	0	0	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	0.9375	likely_pathogenic	0.9517	pathogenic	0.009	Stabilizing	0.985	D	0.559	neutral	None	None	None	None	I
R/C	0.4384	ambiguous	0.5004	ambiguous	-0.314	Destabilizing	1.0	D	0.651	neutral	N	0.494442196	None	None	I
R/D	0.9762	likely_pathogenic	0.9822	pathogenic	-0.366	Destabilizing	0.998	D	0.55	neutral	None	None	None	None	I
R/E	0.8679	likely_pathogenic	0.8928	pathogenic	-0.334	Destabilizing	0.985	D	0.516	neutral	None	None	None	None	I
R/F	0.8908	likely_pathogenic	0.8928	pathogenic	-0.34	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	I
R/G	0.9012	likely_pathogenic	0.9284	pathogenic	-0.109	Destabilizing	0.996	D	0.565	neutral	N	0.485794915	None	None	I
R/H	0.2541	likely_benign	0.259	benign	-0.594	Destabilizing	1.0	D	0.501	neutral	N	0.489460696	None	None	I
R/I	0.6213	likely_pathogenic	0.6548	pathogenic	0.273	Stabilizing	0.999	D	0.604	neutral	None	None	None	None	I
R/K	0.1858	likely_benign	0.1998	benign	-0.242	Destabilizing	0.271	N	0.316	neutral	None	None	None	None	I
R/L	0.6889	likely_pathogenic	0.7177	pathogenic	0.273	Stabilizing	0.996	D	0.565	neutral	N	0.493962438	None	None	I
R/M	0.768	likely_pathogenic	0.7931	pathogenic	-0.145	Destabilizing	1.0	D	0.53	neutral	None	None	None	None	I
R/N	0.9207	likely_pathogenic	0.9363	pathogenic	-0.181	Destabilizing	0.998	D	0.499	neutral	None	None	None	None	I
R/P	0.9916	likely_pathogenic	0.9926	pathogenic	0.201	Stabilizing	1.0	D	0.585	neutral	N	0.512546451	None	None	I
R/Q	0.2753	likely_benign	0.3024	benign	-0.2	Destabilizing	0.996	D	0.513	neutral	None	None	None	None	I
R/S	0.93	likely_pathogenic	0.9482	pathogenic	-0.319	Destabilizing	0.992	D	0.593	neutral	N	0.484129447	None	None	I
R/T	0.8254	likely_pathogenic	0.8565	pathogenic	-0.192	Destabilizing	0.993	D	0.54	neutral	None	None	None	None	I
R/V	0.7806	likely_pathogenic	0.7993	pathogenic	0.201	Stabilizing	0.998	D	0.585	neutral	None	None	None	None	I
R/W	0.4603	ambiguous	0.4701	ambiguous	-0.554	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
R/Y	0.7358	likely_pathogenic	0.7467	pathogenic	-0.157	Destabilizing	0.999	D	0.595	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.