TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18275	55048;55049;55050	chr2:178602579;178602578;178602577	chr2:179467306;179467305;179467304
N2AB	16634	50125;50126;50127	chr2:178602579;178602578;178602577	chr2:179467306;179467305;179467304
N2A	15707	47344;47345;47346	chr2:178602579;178602578;178602577	chr2:179467306;179467305;179467304
N2B	9210	27853;27854;27855	chr2:178602579;178602578;178602577	chr2:179467306;179467305;179467304
Novex-1	9335	28228;28229;28230	chr2:178602579;178602578;178602577	chr2:179467306;179467305;179467304
Novex-2	9402	28429;28430;28431	chr2:178602579;178602578;178602577	chr2:179467306;179467305;179467304
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-21
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2697
• 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
P/A	rs765408419	-1.615	None	N	0.355	0.101	0.12205267543	gnomAD-2.1.1	2.18E-05	None	None	None	None	N	None	0	1.96592E-04	None	0	0	None	0	None	0	0	0
P/A	rs765408419	-1.615	None	N	0.355	0.101	0.12205267543	gnomAD-4.0.0	5.64364E-06	None	None	None	None	N	None	0	1.22249E-04	None	0	0	None	0	0	0	0	0
P/L	None	None	0.027	N	0.636	0.368	0.53046153047	gnomAD-4.0.0	1.87755E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.80044E-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
P/A	0.0962	likely_benign	0.0626	benign	-1.341	Destabilizing	None	N	0.355	neutral	N	0.431107746	None	None	N
P/C	0.505	ambiguous	0.3545	ambiguous	-1.043	Destabilizing	0.824	D	0.804	deleterious	None	None	None	None	N
P/D	0.8399	likely_pathogenic	0.7035	pathogenic	-1.614	Destabilizing	0.149	N	0.679	prob.neutral	None	None	None	None	N
P/E	0.5252	ambiguous	0.3537	ambiguous	-1.687	Destabilizing	0.149	N	0.649	neutral	None	None	None	None	N
P/F	0.6307	likely_pathogenic	0.4646	ambiguous	-1.453	Destabilizing	0.38	N	0.803	deleterious	None	None	None	None	N
P/G	0.5032	ambiguous	0.3282	benign	-1.556	Destabilizing	0.035	N	0.666	neutral	None	None	None	None	N
P/H	0.3682	ambiguous	0.2425	benign	-1.026	Destabilizing	0.824	D	0.791	deleterious	None	None	None	None	N
P/I	0.4184	ambiguous	0.303	benign	-0.876	Destabilizing	0.081	N	0.759	deleterious	None	None	None	None	N
P/K	0.3425	ambiguous	0.2296	benign	-0.981	Destabilizing	0.081	N	0.657	neutral	None	None	None	None	N
P/L	0.257	likely_benign	0.1561	benign	-0.876	Destabilizing	0.027	N	0.636	neutral	N	0.502910168	None	None	N
P/M	0.3996	ambiguous	0.2752	benign	-0.582	Destabilizing	0.007	N	0.483	neutral	None	None	None	None	N
P/N	0.6443	likely_pathogenic	0.4775	ambiguous	-0.796	Destabilizing	0.235	N	0.769	deleterious	None	None	None	None	N
P/Q	0.2711	likely_benign	0.1627	benign	-1.139	Destabilizing	0.317	N	0.713	prob.delet.	N	0.484841912	None	None	N
P/R	0.2794	likely_benign	0.165	benign	-0.352	Destabilizing	0.317	N	0.767	deleterious	N	0.485348891	None	None	N
P/S	0.2124	likely_benign	0.1276	benign	-1.201	Destabilizing	0.002	N	0.391	neutral	N	0.500415903	None	None	N
P/T	0.2422	likely_benign	0.1518	benign	-1.181	Destabilizing	0.062	N	0.639	neutral	N	0.502403189	None	None	N
P/V	0.2984	likely_benign	0.2048	benign	-0.998	Destabilizing	0.035	N	0.677	prob.neutral	None	None	None	None	N
P/W	0.8573	likely_pathogenic	0.7103	pathogenic	-1.523	Destabilizing	0.935	D	0.792	deleterious	None	None	None	None	N
P/Y	0.6325	likely_pathogenic	0.4718	ambiguous	-1.22	Destabilizing	0.555	D	0.808	deleterious	None	None	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.