TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17512	52759;52760;52761	chr2:178608349;178608348;178608347	chr2:179473076;179473075;179473074
N2AB	15871	47836;47837;47838	chr2:178608349;178608348;178608347	chr2:179473076;179473075;179473074
N2A	14944	45055;45056;45057	chr2:178608349;178608348;178608347	chr2:179473076;179473075;179473074
N2B	8447	25564;25565;25566	chr2:178608349;178608348;178608347	chr2:179473076;179473075;179473074
Novex-1	8572	25939;25940;25941	chr2:178608349;178608348;178608347	chr2:179473076;179473075;179473074
Novex-2	8639	26140;26141;26142	chr2:178608349;178608348;178608347	chr2:179473076;179473075;179473074
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-15
• Domain position: 43
• Structural Position: 51
• Q(SASA): 0.9413
• 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/D	rs528550177	0.39	0.896	N	0.43	0.323	0.244539031024	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	1.47E-05	0	0
N/D	rs528550177	0.39	0.896	N	0.43	0.323	0.244539031024	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
N/D	rs528550177	0.39	0.896	N	0.43	0.323	0.244539031024	gnomAD-4.0.0	3.85025E-06	None	None	None	None	N	None	0	1.69774E-05	None	0	0	None	0	0	2.39676E-06	0	2.84933E-05
N/I	rs1446942544	0.242	0.984	N	0.586	0.535	0.546780063783	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
N/I	rs1446942544	0.242	0.984	N	0.586	0.535	0.546780063783	gnomAD-4.0.0	1.5946E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43505E-05	0
N/K	rs199615557	0.483	0.026	N	0.278	0.1	0.0666544352282	gnomAD-2.1.1	3.23732E-04	None	None	None	None	N	None	8.3E-05	0	None	0	0	None	0	None	0	6.93186E-04	0
N/K	rs199615557	0.483	0.026	N	0.278	0.1	0.0666544352282	gnomAD-3.1.2	3.48905E-04	None	None	None	None	N	None	1.93283E-04	1.31251E-04	0	0	0	None	9.43E-05	0	6.18284E-04	0	0
N/K	rs199615557	0.483	0.026	N	0.278	0.1	0.0666544352282	gnomAD-4.0.0	5.21035E-04	None	None	None	None	N	None	1.20112E-04	5.01169E-05	None	0	0	None	7.82669E-05	0	6.88657E-04	0	1.76322E-04
N/S	rs1446942544	0.266	0.896	N	0.455	0.318	0.228597637076	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
N/S	rs1446942544	0.266	0.896	N	0.455	0.318	0.228597637076	gnomAD-4.0.0	1.5946E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03196E-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
N/A	0.6296	likely_pathogenic	0.5245	ambiguous	-0.165	Destabilizing	0.919	D	0.443	neutral	None	None	None	None	N
N/C	0.6772	likely_pathogenic	0.6058	pathogenic	0.124	Stabilizing	0.999	D	0.657	neutral	None	None	None	None	N
N/D	0.5725	likely_pathogenic	0.4385	ambiguous	0.016	Stabilizing	0.896	D	0.43	neutral	N	0.482328788	None	None	N
N/E	0.8864	likely_pathogenic	0.778	pathogenic	-0.053	Destabilizing	0.851	D	0.413	neutral	None	None	None	None	N
N/F	0.8726	likely_pathogenic	0.8265	pathogenic	-0.777	Destabilizing	0.996	D	0.575	neutral	None	None	None	None	N
N/G	0.5587	ambiguous	0.4581	ambiguous	-0.241	Destabilizing	0.919	D	0.397	neutral	None	None	None	None	N
N/H	0.3121	likely_benign	0.2418	benign	-0.259	Destabilizing	0.984	D	0.401	neutral	N	0.480121878	None	None	N
N/I	0.7479	likely_pathogenic	0.6676	pathogenic	-0.062	Destabilizing	0.984	D	0.586	neutral	N	0.485806644	None	None	N
N/K	0.8072	likely_pathogenic	0.6827	pathogenic	0.12	Stabilizing	0.026	N	0.278	neutral	N	0.473730734	None	None	N
N/L	0.6146	likely_pathogenic	0.512	ambiguous	-0.062	Destabilizing	0.976	D	0.472	neutral	None	None	None	None	N
N/M	0.7237	likely_pathogenic	0.6436	pathogenic	0.106	Stabilizing	0.999	D	0.539	neutral	None	None	None	None	N
N/P	0.9128	likely_pathogenic	0.8678	pathogenic	-0.075	Destabilizing	0.988	D	0.535	neutral	None	None	None	None	N
N/Q	0.7566	likely_pathogenic	0.6382	pathogenic	-0.328	Destabilizing	0.507	D	0.27	neutral	None	None	None	None	N
N/R	0.7561	likely_pathogenic	0.6691	pathogenic	0.206	Stabilizing	0.851	D	0.383	neutral	None	None	None	None	N
N/S	0.1845	likely_benign	0.1585	benign	-0.076	Destabilizing	0.896	D	0.455	neutral	N	0.474018735	None	None	N
N/T	0.397	ambiguous	0.3152	benign	-0.036	Destabilizing	0.896	D	0.393	neutral	N	0.485313165	None	None	N
N/V	0.7505	likely_pathogenic	0.6695	pathogenic	-0.075	Destabilizing	0.988	D	0.575	neutral	None	None	None	None	N
N/W	0.9467	likely_pathogenic	0.9333	pathogenic	-0.893	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
N/Y	0.4928	ambiguous	0.4301	ambiguous	-0.577	Destabilizing	0.995	D	0.535	neutral	N	0.489592079	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.