TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8961	27106;27107;27108	chr2:178713253;178713252;178713251	chr2:179577980;179577979;179577978
N2AB	8644	26155;26156;26157	chr2:178713253;178713252;178713251	chr2:179577980;179577979;179577978
N2A	7717	23374;23375;23376	chr2:178713253;178713252;178713251	chr2:179577980;179577979;179577978
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-75
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1965
• 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
H/P	None	None	0.975	N	0.657	0.304	0.294918367191	gnomAD-4.0.0	6.84649E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99855E-07	0	0
H/R	rs766862084	-1.345	0.006	N	0.222	0.154	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
H/R	rs766862084	-1.345	0.006	N	0.222	0.154	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
H/R	rs766862084	-1.345	0.006	N	0.222	0.154	None	gnomAD-4.0.0	6.88266E-05	None	None	None	None	N	None	1.33511E-05	1.67056E-05	None	0	0	None	0	0	7.63162E-05	1.32045E-04	1.1214E-04
H/Y	rs2076926371	None	0.002	N	0.219	0.111	0.139678290688	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
H/Y	rs2076926371	None	0.002	N	0.219	0.111	0.139678290688	gnomAD-4.0.0	6.57566E-06	None	None	None	None	N	None	2.41523E-05	0	None	0	0	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
H/A	0.5266	ambiguous	0.5874	pathogenic	-1.479	Destabilizing	0.495	N	0.47	neutral	None	None	None	None	N
H/C	0.2093	likely_benign	0.2583	benign	-0.89	Destabilizing	0.995	D	0.656	neutral	None	None	None	None	N
H/D	0.6078	likely_pathogenic	0.696	pathogenic	-1.229	Destabilizing	0.784	D	0.559	neutral	N	0.481354013	None	None	N
H/E	0.4845	ambiguous	0.5673	pathogenic	-1.049	Destabilizing	0.495	N	0.424	neutral	None	None	None	None	N
H/F	0.3554	ambiguous	0.392	ambiguous	0.112	Stabilizing	0.007	N	0.333	neutral	None	None	None	None	N
H/G	0.5991	likely_pathogenic	0.6724	pathogenic	-1.903	Destabilizing	0.665	D	0.524	neutral	None	None	None	None	N
H/I	0.4509	ambiguous	0.5133	ambiguous	-0.243	Destabilizing	0.543	D	0.649	neutral	None	None	None	None	N
H/K	0.2124	likely_benign	0.2415	benign	-0.793	Destabilizing	0.013	N	0.293	neutral	None	None	None	None	N
H/L	0.1604	likely_benign	0.181	benign	-0.243	Destabilizing	0.27	N	0.497	neutral	N	0.453840172	None	None	N
H/M	0.5948	likely_pathogenic	0.619	pathogenic	-0.536	Destabilizing	0.944	D	0.623	neutral	None	None	None	None	N
H/N	0.2818	likely_benign	0.352	ambiguous	-1.387	Destabilizing	0.642	D	0.458	neutral	N	0.508368091	None	None	N
H/P	0.7674	likely_pathogenic	0.8115	pathogenic	-0.642	Destabilizing	0.975	D	0.657	neutral	N	0.489512971	None	None	N
H/Q	0.1897	likely_benign	0.2219	benign	-1.035	Destabilizing	0.642	D	0.499	neutral	N	0.485933948	None	None	N
H/R	0.0765	likely_benign	0.0926	benign	-0.932	Destabilizing	0.006	N	0.222	neutral	N	0.394733154	None	None	N
H/S	0.4551	ambiguous	0.5224	ambiguous	-1.609	Destabilizing	0.495	N	0.477	neutral	None	None	None	None	N
H/T	0.5681	likely_pathogenic	0.6394	pathogenic	-1.303	Destabilizing	0.828	D	0.567	neutral	None	None	None	None	N
H/V	0.406	ambiguous	0.4543	ambiguous	-0.642	Destabilizing	0.704	D	0.565	neutral	None	None	None	None	N
H/W	0.3796	ambiguous	0.4038	ambiguous	0.657	Stabilizing	0.985	D	0.625	neutral	None	None	None	None	N
H/Y	0.1208	likely_benign	0.1402	benign	0.599	Stabilizing	0.002	N	0.219	neutral	N	0.468521623	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.