TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17380	52363;52364;52365	chr2:178608873;178608872;178608871	chr2:179473600;179473599;179473598
N2AB	15739	47440;47441;47442	chr2:178608873;178608872;178608871	chr2:179473600;179473599;179473598
N2A	14812	44659;44660;44661	chr2:178608873;178608872;178608871	chr2:179473600;179473599;179473598
N2B	8315	25168;25169;25170	chr2:178608873;178608872;178608871	chr2:179473600;179473599;179473598
Novex-1	8440	25543;25544;25545	chr2:178608873;178608872;178608871	chr2:179473600;179473599;179473598
Novex-2	8507	25744;25745;25746	chr2:178608873;178608872;178608871	chr2:179473600;179473599;179473598
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-14
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.519
• 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
D/G	rs373305248	-0.575	0.822	N	0.548	0.415	0.213573922156	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	2.9E-05	None	0	5.6E-05	None	0	None	0	0	0
D/G	rs373305248	-0.575	0.822	N	0.548	0.415	0.213573922156	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94628E-04	None	0	0	0	0	0
D/G	rs373305248	-0.575	0.822	N	0.548	0.415	0.213573922156	gnomAD-4.0.0	2.48228E-06	None	None	None	None	N	None	0	1.668E-05	None	0	4.47227E-05	None	0	0	0	1.0983E-05	0
D/N	rs886042593	None	0.822	N	0.541	0.295	0.187945064343	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	4.78927E-04
D/N	rs886042593	None	0.822	N	0.541	0.295	0.187945064343	gnomAD-4.0.0	1.316E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47184E-05	0	4.78927E-04
D/V	rs373305248	0.412	0.942	N	0.642	0.504	None	gnomAD-2.1.1	7.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.41101E-04	2.82008E-04
D/V	rs373305248	0.412	0.942	N	0.642	0.504	None	gnomAD-3.1.2	7.24E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.61893E-04	0	0
D/V	rs373305248	0.412	0.942	N	0.642	0.504	None	gnomAD-4.0.0	9.30923E-05	None	None	None	None	N	None	1.33665E-05	1.66856E-05	None	0	0	None	0	0	1.24662E-04	0	1.60308E-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
D/A	0.352	ambiguous	0.2745	benign	-0.339	Destabilizing	0.698	D	0.509	neutral	N	0.500029114	None	None	N
D/C	0.8345	likely_pathogenic	0.7529	pathogenic	-0.165	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
D/E	0.1762	likely_benign	0.135	benign	-0.379	Destabilizing	0.006	N	0.181	neutral	N	0.392861576	None	None	N
D/F	0.8338	likely_pathogenic	0.7542	pathogenic	-0.054	Destabilizing	0.993	D	0.651	neutral	None	None	None	None	N
D/G	0.2947	likely_benign	0.2356	benign	-0.587	Destabilizing	0.822	D	0.548	neutral	N	0.513921131	None	None	N
D/H	0.5831	likely_pathogenic	0.4679	ambiguous	0.048	Stabilizing	0.992	D	0.59	neutral	N	0.46913074	None	None	N
D/I	0.6852	likely_pathogenic	0.5567	ambiguous	0.282	Stabilizing	0.978	D	0.664	neutral	None	None	None	None	N
D/K	0.6535	likely_pathogenic	0.5423	ambiguous	0.121	Stabilizing	0.754	D	0.515	neutral	None	None	None	None	N
D/L	0.6889	likely_pathogenic	0.5748	pathogenic	0.282	Stabilizing	0.956	D	0.645	neutral	None	None	None	None	N
D/M	0.7878	likely_pathogenic	0.6876	pathogenic	0.358	Stabilizing	0.998	D	0.626	neutral	None	None	None	None	N
D/N	0.1615	likely_benign	0.1348	benign	-0.305	Destabilizing	0.822	D	0.541	neutral	N	0.488908043	None	None	N
D/P	0.9539	likely_pathogenic	0.9077	pathogenic	0.099	Stabilizing	0.978	D	0.591	neutral	None	None	None	None	N
D/Q	0.5587	ambiguous	0.4488	ambiguous	-0.235	Destabilizing	0.915	D	0.531	neutral	None	None	None	None	N
D/R	0.7298	likely_pathogenic	0.6271	pathogenic	0.372	Stabilizing	0.956	D	0.597	neutral	None	None	None	None	N
D/S	0.2724	likely_benign	0.2109	benign	-0.429	Destabilizing	0.754	D	0.461	neutral	None	None	None	None	N
D/T	0.4425	ambiguous	0.3517	ambiguous	-0.23	Destabilizing	0.956	D	0.555	neutral	None	None	None	None	N
D/V	0.4635	ambiguous	0.3527	ambiguous	0.099	Stabilizing	0.942	D	0.642	neutral	N	0.469509134	None	None	N
D/W	0.953	likely_pathogenic	0.9213	pathogenic	0.132	Stabilizing	0.998	D	0.631	neutral	None	None	None	None	N
D/Y	0.4681	ambiguous	0.3733	ambiguous	0.193	Stabilizing	0.99	D	0.652	neutral	N	0.495628786	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.