TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17889	53890;53891;53892	chr2:178605630;178605629;178605628	chr2:179470357;179470356;179470355
N2AB	16248	48967;48968;48969	chr2:178605630;178605629;178605628	chr2:179470357;179470356;179470355
N2A	15321	46186;46187;46188	chr2:178605630;178605629;178605628	chr2:179470357;179470356;179470355
N2B	8824	26695;26696;26697	chr2:178605630;178605629;178605628	chr2:179470357;179470356;179470355
Novex-1	8949	27070;27071;27072	chr2:178605630;178605629;178605628	chr2:179470357;179470356;179470355
Novex-2	9016	27271;27272;27273	chr2:178605630;178605629;178605628	chr2:179470357;179470356;179470355
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: Fn3-18
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.4243
• 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
N/H	None	None	0.295	N	0.396	0.08	0.195762928549	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
N/S	rs1457628589	-0.492	0.005	N	0.167	0.165	0.208816687407	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
N/S	rs1457628589	-0.492	0.005	N	0.167	0.165	0.208816687407	gnomAD-4.0.0	1.6413E-06	None	None	None	None	I	None	0	0	None	0	2.87803E-05	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
N/A	0.4181	ambiguous	0.3854	ambiguous	-0.696	Destabilizing	0.031	N	0.465	neutral	None	None	None	None	I
N/C	0.5592	ambiguous	0.5191	ambiguous	0.126	Stabilizing	0.864	D	0.468	neutral	None	None	None	None	I
N/D	0.0603	likely_benign	0.0561	benign	-0.618	Destabilizing	None	N	0.077	neutral	N	0.337333581	None	None	I
N/E	0.6779	likely_pathogenic	0.6493	pathogenic	-0.602	Destabilizing	0.003	N	0.16	neutral	None	None	None	None	I
N/F	0.855	likely_pathogenic	0.8367	pathogenic	-0.937	Destabilizing	0.628	D	0.479	neutral	None	None	None	None	I
N/G	0.4848	ambiguous	0.4027	ambiguous	-0.932	Destabilizing	0.014	N	0.155	neutral	None	None	None	None	I
N/H	0.3099	likely_benign	0.3144	benign	-0.989	Destabilizing	0.295	N	0.396	neutral	N	0.481712712	None	None	I
N/I	0.642	likely_pathogenic	0.6275	pathogenic	-0.138	Destabilizing	0.295	N	0.496	neutral	N	0.475056099	None	None	I
N/K	0.7436	likely_pathogenic	0.749	pathogenic	-0.046	Destabilizing	0.024	N	0.255	neutral	N	0.513438341	None	None	I
N/L	0.5923	likely_pathogenic	0.5462	ambiguous	-0.138	Destabilizing	0.072	N	0.507	neutral	None	None	None	None	I
N/M	0.7035	likely_pathogenic	0.6737	pathogenic	0.531	Stabilizing	0.628	D	0.45	neutral	None	None	None	None	I
N/P	0.7733	likely_pathogenic	0.7244	pathogenic	-0.297	Destabilizing	0.136	N	0.481	neutral	None	None	None	None	I
N/Q	0.6794	likely_pathogenic	0.654	pathogenic	-0.784	Destabilizing	0.072	N	0.259	neutral	None	None	None	None	I
N/R	0.7326	likely_pathogenic	0.7326	pathogenic	0.04	Stabilizing	0.072	N	0.265	neutral	None	None	None	None	I
N/S	0.1069	likely_benign	0.1029	benign	-0.508	Destabilizing	0.005	N	0.167	neutral	N	0.44694399	None	None	I
N/T	0.1867	likely_benign	0.1768	benign	-0.328	Destabilizing	0.024	N	0.26	neutral	N	0.447925425	None	None	I
N/V	0.5604	ambiguous	0.5288	ambiguous	-0.297	Destabilizing	0.136	N	0.503	neutral	None	None	None	None	I
N/W	0.942	likely_pathogenic	0.9395	pathogenic	-0.775	Destabilizing	0.864	D	0.505	neutral	None	None	None	None	I
N/Y	0.4516	ambiguous	0.4458	ambiguous	-0.521	Destabilizing	0.56	D	0.465	neutral	N	0.477711887	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.