TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29905	89938;89939;89940	chr2:178553187;178553186;178553185	chr2:179417914;179417913;179417912
N2AB	28264	85015;85016;85017	chr2:178553187;178553186;178553185	chr2:179417914;179417913;179417912
N2A	27337	82234;82235;82236	chr2:178553187;178553186;178553185	chr2:179417914;179417913;179417912
N2B	20840	62743;62744;62745	chr2:178553187;178553186;178553185	chr2:179417914;179417913;179417912
Novex-1	20965	63118;63119;63120	chr2:178553187;178553186;178553185	chr2:179417914;179417913;179417912
Novex-2	21032	63319;63320;63321	chr2:178553187;178553186;178553185	chr2:179417914;179417913;179417912
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-147
• Domain position: 64
• Structural Position: 148
• Q(SASA): 0.4315
• 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
N/S	rs773727575	0.386	0.052	N	0.268	0.116	0.0762999501168	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/S	rs773727575	0.386	0.052	N	0.268	0.116	0.0762999501168	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs773727575	0.386	0.052	N	0.268	0.116	0.0762999501168	gnomAD-4.0.0	5.12376E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.39273E-06	4.02015E-05	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
N/A	0.1567	likely_benign	0.1391	benign	-0.23	Destabilizing	0.149	N	0.323	neutral	None	None	None	None	N
N/C	0.249	likely_benign	0.2311	benign	0.425	Stabilizing	0.935	D	0.393	neutral	None	None	None	None	N
N/D	0.0952	likely_benign	0.0832	benign	0.033	Stabilizing	None	N	0.1	neutral	N	0.393773148	None	None	N
N/E	0.2137	likely_benign	0.1747	benign	-0.027	Destabilizing	0.002	N	0.122	neutral	None	None	None	None	N
N/F	0.3518	ambiguous	0.3159	benign	-0.749	Destabilizing	0.38	N	0.373	neutral	None	None	None	None	N
N/G	0.2242	likely_benign	0.2016	benign	-0.353	Destabilizing	0.067	N	0.235	neutral	None	None	None	None	N
N/H	0.0832	likely_benign	0.078	benign	-0.45	Destabilizing	0.001	N	0.197	neutral	N	0.480162769	None	None	N
N/I	0.1791	likely_benign	0.1672	benign	0.001	Stabilizing	0.484	N	0.387	neutral	N	0.502596911	None	None	N
N/K	0.1883	likely_benign	0.1646	benign	0.188	Stabilizing	0.117	N	0.203	neutral	N	0.448954428	None	None	N
N/L	0.17	likely_benign	0.1471	benign	0.001	Stabilizing	0.149	N	0.355	neutral	None	None	None	None	N
N/M	0.2425	likely_benign	0.217	benign	0.387	Stabilizing	0.935	D	0.347	neutral	None	None	None	None	N
N/P	0.7445	likely_pathogenic	0.6982	pathogenic	-0.052	Destabilizing	0.555	D	0.356	neutral	None	None	None	None	N
N/Q	0.2003	likely_benign	0.1736	benign	-0.22	Destabilizing	0.149	N	0.289	neutral	None	None	None	None	N
N/R	0.2294	likely_benign	0.1938	benign	0.268	Stabilizing	0.149	N	0.29	neutral	None	None	None	None	N
N/S	0.0791	likely_benign	0.0761	benign	0.049	Stabilizing	0.052	N	0.268	neutral	N	0.420399602	None	None	N
N/T	0.1093	likely_benign	0.1043	benign	0.111	Stabilizing	0.117	N	0.209	neutral	N	0.451282657	None	None	N
N/V	0.1897	likely_benign	0.1683	benign	-0.052	Destabilizing	0.555	D	0.347	neutral	None	None	None	None	N
N/W	0.5693	likely_pathogenic	0.5079	ambiguous	-0.803	Destabilizing	0.935	D	0.498	neutral	None	None	None	None	N
N/Y	0.1076	likely_benign	0.0999	benign	-0.509	Destabilizing	0.188	N	0.371	neutral	N	0.431486175	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.