TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23109	69550;69551;69552	chr2:178577010;178577009;178577008	chr2:179441737;179441736;179441735
N2AB	21468	64627;64628;64629	chr2:178577010;178577009;178577008	chr2:179441737;179441736;179441735
N2A	20541	61846;61847;61848	chr2:178577010;178577009;178577008	chr2:179441737;179441736;179441735
N2B	14044	42355;42356;42357	chr2:178577010;178577009;178577008	chr2:179441737;179441736;179441735
Novex-1	14169	42730;42731;42732	chr2:178577010;178577009;178577008	chr2:179441737;179441736;179441735
Novex-2	14236	42931;42932;42933	chr2:178577010;178577009;178577008	chr2:179441737;179441736;179441735
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-55
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.2964
• 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
E/A	rs1212757037	-1.211	0.958	N	0.648	0.511	0.418344901717	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/A	rs1212757037	-1.211	0.958	N	0.648	0.511	0.418344901717	gnomAD-4.0.0	1.36865E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79922E-06	0	0
E/D	None	None	0.067	N	0.205	0.181	0.280987212366	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41546E-04	0	0	0
E/K	rs727503571	None	0.958	N	0.549	0.345	0.377097596864	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.55E-05	0	0	1.93648E-04	None	0	0	0	0	0
E/K	rs727503571	None	0.958	N	0.549	0.345	0.377097596864	gnomAD-4.0.0	3.04523E-06	None	None	None	None	N	None	0	6.15536E-05	None	0	1.13714E-04	None	0	0	1.205E-06	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
E/A	0.7244	likely_pathogenic	0.6653	pathogenic	-0.94	Destabilizing	0.958	D	0.648	neutral	N	0.49166554	None	None	N
E/C	0.9821	likely_pathogenic	0.9758	pathogenic	-0.556	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/D	0.7415	likely_pathogenic	0.6897	pathogenic	-1.322	Destabilizing	0.067	N	0.205	neutral	N	0.488689799	None	None	N
E/F	0.9905	likely_pathogenic	0.9883	pathogenic	-0.273	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/G	0.856	likely_pathogenic	0.8209	pathogenic	-1.366	Destabilizing	0.988	D	0.734	prob.delet.	N	0.497198948	None	None	N
E/H	0.9486	likely_pathogenic	0.9301	pathogenic	-0.653	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/I	0.8981	likely_pathogenic	0.8798	pathogenic	0.245	Stabilizing	0.995	D	0.817	deleterious	None	None	None	None	N
E/K	0.7478	likely_pathogenic	0.7347	pathogenic	-0.914	Destabilizing	0.958	D	0.549	neutral	N	0.478281318	None	None	N
E/L	0.9463	likely_pathogenic	0.9331	pathogenic	0.245	Stabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
E/M	0.9219	likely_pathogenic	0.9068	pathogenic	0.819	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/N	0.8699	likely_pathogenic	0.827	pathogenic	-1.409	Destabilizing	0.982	D	0.731	prob.delet.	None	None	None	None	N
E/P	0.9897	likely_pathogenic	0.987	pathogenic	-0.129	Destabilizing	0.995	D	0.828	deleterious	None	None	None	None	N
E/Q	0.4922	ambiguous	0.4271	ambiguous	-1.204	Destabilizing	0.994	D	0.671	neutral	N	0.470901485	None	None	N
E/R	0.8401	likely_pathogenic	0.814	pathogenic	-0.667	Destabilizing	0.995	D	0.763	deleterious	None	None	None	None	N
E/S	0.7624	likely_pathogenic	0.6932	pathogenic	-1.834	Destabilizing	0.968	D	0.588	neutral	None	None	None	None	N
E/T	0.7537	likely_pathogenic	0.7133	pathogenic	-1.469	Destabilizing	0.991	D	0.771	deleterious	None	None	None	None	N
E/V	0.8033	likely_pathogenic	0.7657	pathogenic	-0.129	Destabilizing	0.994	D	0.791	deleterious	N	0.480664856	None	None	N
E/W	0.9967	likely_pathogenic	0.9955	pathogenic	-0.056	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Y	0.9788	likely_pathogenic	0.9753	pathogenic	-0.025	Destabilizing	1.0	D	0.807	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.