TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20425	61498;61499;61500	chr2:178590452;178590451;178590450	chr2:179455179;179455178;179455177
N2AB	18784	56575;56576;56577	chr2:178590452;178590451;178590450	chr2:179455179;179455178;179455177
N2A	17857	53794;53795;53796	chr2:178590452;178590451;178590450	chr2:179455179;179455178;179455177
N2B	11360	34303;34304;34305	chr2:178590452;178590451;178590450	chr2:179455179;179455178;179455177
Novex-1	11485	34678;34679;34680	chr2:178590452;178590451;178590450	chr2:179455179;179455178;179455177
Novex-2	11552	34879;34880;34881	chr2:178590452;178590451;178590450	chr2:179455179;179455178;179455177
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-36
• Domain position: 55
• Structural Position: 74
• Q(SASA): 0.644
• 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
E/D	rs1252644947	0.112	0.001	N	0.143	0.044	0.12205267543	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	1.67954E-04	None	0	None	0	0	0
E/D	rs1252644947	0.112	0.001	N	0.143	0.044	0.12205267543	gnomAD-4.0.0	6.37196E-06	None	None	None	None	I	None	0	0	None	0	1.11191E-04	None	0	0	0	0	0
E/G	rs1471584816	-0.264	0.521	N	0.435	0.294	0.289847578895	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
E/G	rs1471584816	-0.264	0.521	N	0.435	0.294	0.289847578895	gnomAD-4.0.0	1.59294E-06	None	None	None	None	I	None	0	0	None	0	2.77994E-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
E/A	0.201	likely_benign	0.2108	benign	-0.166	Destabilizing	0.007	N	0.279	neutral	N	0.496911451	None	None	I
E/C	0.8263	likely_pathogenic	0.8486	pathogenic	-0.034	Destabilizing	0.987	D	0.409	neutral	None	None	None	None	I
E/D	0.1014	likely_benign	0.1062	benign	-0.184	Destabilizing	0.001	N	0.143	neutral	N	0.446312059	None	None	I
E/F	0.7992	likely_pathogenic	0.7998	pathogenic	-0.15	Destabilizing	0.953	D	0.396	neutral	None	None	None	None	I
E/G	0.2182	likely_benign	0.2196	benign	-0.32	Destabilizing	0.521	D	0.435	neutral	N	0.514457062	None	None	I
E/H	0.4877	ambiguous	0.484	ambiguous	0.237	Stabilizing	0.984	D	0.325	neutral	None	None	None	None	I
E/I	0.4474	ambiguous	0.4354	ambiguous	0.191	Stabilizing	0.91	D	0.415	neutral	None	None	None	None	I
E/K	0.2185	likely_benign	0.204	benign	0.414	Stabilizing	0.684	D	0.437	neutral	N	0.506339011	None	None	I
E/L	0.5213	ambiguous	0.5293	ambiguous	0.191	Stabilizing	0.59	D	0.422	neutral	None	None	None	None	I
E/M	0.5489	ambiguous	0.5648	pathogenic	0.133	Stabilizing	0.996	D	0.385	neutral	None	None	None	None	I
E/N	0.2456	likely_benign	0.2515	benign	0.194	Stabilizing	0.59	D	0.394	neutral	None	None	None	None	I
E/P	0.7952	likely_pathogenic	0.7848	pathogenic	0.092	Stabilizing	0.953	D	0.37	neutral	None	None	None	None	I
E/Q	0.1704	likely_benign	0.1706	benign	0.219	Stabilizing	0.815	D	0.415	neutral	D	0.522809973	None	None	I
E/R	0.3567	ambiguous	0.3414	ambiguous	0.606	Stabilizing	0.953	D	0.357	neutral	None	None	None	None	I
E/S	0.232	likely_benign	0.237	benign	0.029	Stabilizing	0.59	D	0.387	neutral	None	None	None	None	I
E/T	0.2256	likely_benign	0.2365	benign	0.157	Stabilizing	0.742	D	0.412	neutral	None	None	None	None	I
E/V	0.2688	likely_benign	0.2692	benign	0.092	Stabilizing	0.521	D	0.421	neutral	N	0.474037378	None	None	I
E/W	0.9264	likely_pathogenic	0.9275	pathogenic	-0.064	Destabilizing	0.996	D	0.531	neutral	None	None	None	None	I
E/Y	0.6534	likely_pathogenic	0.6512	pathogenic	0.08	Stabilizing	0.984	D	0.395	neutral	None	None	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.