TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27298	82117;82118;82119	chr2:178564240;178564239;178564238	chr2:179428967;179428966;179428965
N2AB	25657	77194;77195;77196	chr2:178564240;178564239;178564238	chr2:179428967;179428966;179428965
N2A	24730	74413;74414;74415	chr2:178564240;178564239;178564238	chr2:179428967;179428966;179428965
N2B	18233	54922;54923;54924	chr2:178564240;178564239;178564238	chr2:179428967;179428966;179428965
Novex-1	18358	55297;55298;55299	chr2:178564240;178564239;178564238	chr2:179428967;179428966;179428965
Novex-2	18425	55498;55499;55500	chr2:178564240;178564239;178564238	chr2:179428967;179428966;179428965
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-140
• Domain position: 21
• Structural Position: 34
• Q(SASA): 0.4762
• 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
D/A	rs557375464	-0.445	1.0	N	0.753	0.479	0.52991035303	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
D/A	rs557375464	-0.445	1.0	N	0.753	0.479	0.52991035303	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.06782E-04	0
D/A	rs557375464	-0.445	1.0	N	0.753	0.479	0.52991035303	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
D/A	rs557375464	-0.445	1.0	N	0.753	0.479	0.52991035303	gnomAD-4.0.0	6.56737E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.06954E-04	0
D/G	None	None	1.0	D	0.762	0.518	0.473378105536	gnomAD-4.0.0	1.59237E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-05	0
D/N	rs200697681	-0.832	1.0	D	0.673	0.411	None	gnomAD-2.1.1	2.79264E-04	None	None	None	None	I	None	8.27E-05	1.18792E-03	None	0	0	None	0	None	0	2.43084E-04	4.21585E-04
D/N	rs200697681	-0.832	1.0	D	0.673	0.411	None	gnomAD-3.1.2	1.64344E-04	None	None	None	None	I	None	9.65E-05	3.93339E-04	0	5.77367E-04	0	None	0	0	1.76419E-04	2.07125E-04	0
D/N	rs200697681	-0.832	1.0	D	0.673	0.411	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
D/N	rs200697681	-0.832	1.0	D	0.673	0.411	None	gnomAD-4.0.0	1.59925E-04	None	None	None	None	I	None	7.99659E-05	8.66753E-04	None	6.75813E-05	2.22916E-05	None	0	0	1.57657E-04	1.09796E-05	1.60056E-04

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
D/A	0.215	likely_benign	0.2541	benign	-0.294	Destabilizing	1.0	D	0.753	deleterious	N	0.488324545	None	None	I
D/C	0.692	likely_pathogenic	0.7416	pathogenic	-0.14	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
D/E	0.276	likely_benign	0.308	benign	-0.381	Destabilizing	1.0	D	0.453	neutral	N	0.499040184	None	None	I
D/F	0.6298	likely_pathogenic	0.6587	pathogenic	-0.126	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
D/G	0.2583	likely_benign	0.297	benign	-0.525	Destabilizing	1.0	D	0.762	deleterious	D	0.529672522	None	None	I
D/H	0.3646	ambiguous	0.4093	ambiguous	-0.041	Destabilizing	1.0	D	0.749	deleterious	N	0.51666594	None	None	I
D/I	0.4168	ambiguous	0.4552	ambiguous	0.273	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
D/K	0.5564	ambiguous	0.6149	pathogenic	0.03	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
D/L	0.4763	ambiguous	0.5265	ambiguous	0.273	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
D/M	0.6558	likely_pathogenic	0.6914	pathogenic	0.341	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
D/N	0.1183	likely_benign	0.1268	benign	-0.237	Destabilizing	1.0	D	0.673	neutral	D	0.528632372	None	None	I
D/P	0.912	likely_pathogenic	0.9272	pathogenic	0.107	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
D/Q	0.4902	ambiguous	0.5477	ambiguous	-0.189	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
D/R	0.566	likely_pathogenic	0.6174	pathogenic	0.271	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
D/S	0.1774	likely_benign	0.1889	benign	-0.383	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
D/T	0.3253	likely_benign	0.3631	ambiguous	-0.209	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
D/V	0.2551	likely_benign	0.2878	benign	0.107	Stabilizing	1.0	D	0.787	deleterious	N	0.497618819	None	None	I
D/W	0.9067	likely_pathogenic	0.917	pathogenic	0.011	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
D/Y	0.2703	likely_benign	0.3026	benign	0.101	Stabilizing	1.0	D	0.769	deleterious	N	0.498899194	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.