TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6595	20008;20009;20010	chr2:178727795;178727794;178727793	chr2:179592522;179592521;179592520
N2AB	6278	19057;19058;19059	chr2:178727795;178727794;178727793	chr2:179592522;179592521;179592520
N2A	5351	16276;16277;16278	chr2:178727795;178727794;178727793	chr2:179592522;179592521;179592520
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-50
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1213
• 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
A/T	rs1305423472	-1.364	0.811	N	0.702	0.254	0.273503213844	gnomAD-2.1.1	7.16E-06	None	None	None	None	N	None	0	0	None	0	5.13E-05	None	0	None	4.01E-05	0	0
A/T	rs1305423472	-1.364	0.811	N	0.702	0.254	0.273503213844	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
A/T	rs1305423472	-1.364	0.811	N	0.702	0.254	0.273503213844	gnomAD-4.0.0	2.48042E-06	None	None	None	None	N	None	0	0	None	0	4.45891E-05	None	1.56284E-05	0	8.48043E-07	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
A/C	0.5426	ambiguous	0.5773	pathogenic	-0.329	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
A/D	0.8618	likely_pathogenic	0.8877	pathogenic	-1.718	Destabilizing	0.976	D	0.801	deleterious	None	None	None	None	N
A/E	0.8543	likely_pathogenic	0.8785	pathogenic	-1.481	Destabilizing	0.968	D	0.801	deleterious	N	0.466683252	None	None	N
A/F	0.6981	likely_pathogenic	0.7324	pathogenic	-0.332	Destabilizing	0.988	D	0.821	deleterious	None	None	None	None	N
A/G	0.1763	likely_benign	0.1855	benign	-1.169	Destabilizing	0.011	N	0.406	neutral	N	0.452381522	None	None	N
A/H	0.9215	likely_pathogenic	0.9391	pathogenic	-1.779	Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
A/I	0.4334	ambiguous	0.4703	ambiguous	0.715	Stabilizing	0.952	D	0.799	deleterious	None	None	None	None	N
A/K	0.9663	likely_pathogenic	0.976	pathogenic	-0.557	Destabilizing	0.976	D	0.795	deleterious	None	None	None	None	N
A/L	0.3898	ambiguous	0.4149	ambiguous	0.715	Stabilizing	0.851	D	0.757	deleterious	None	None	None	None	N
A/M	0.4001	ambiguous	0.4307	ambiguous	0.492	Stabilizing	0.997	D	0.776	deleterious	None	None	None	None	N
A/N	0.6973	likely_pathogenic	0.74	pathogenic	-0.915	Destabilizing	0.976	D	0.816	deleterious	None	None	None	None	N
A/P	0.9137	likely_pathogenic	0.9399	pathogenic	0.299	Stabilizing	0.984	D	0.787	deleterious	N	0.466683252	None	None	N
A/Q	0.8806	likely_pathogenic	0.908	pathogenic	-0.621	Destabilizing	0.988	D	0.766	deleterious	None	None	None	None	N
A/R	0.9437	likely_pathogenic	0.9552	pathogenic	-0.915	Destabilizing	0.988	D	0.785	deleterious	None	None	None	None	N
A/S	0.1419	likely_benign	0.1548	benign	-1.314	Destabilizing	0.437	N	0.436	neutral	N	0.412881771	None	None	N
A/T	0.112	likely_benign	0.123	benign	-0.943	Destabilizing	0.811	D	0.702	prob.neutral	N	0.500519398	None	None	N
A/V	0.176	likely_benign	0.1958	benign	0.299	Stabilizing	0.059	N	0.467	neutral	N	0.413358987	None	None	N
A/W	0.9568	likely_pathogenic	0.9663	pathogenic	-1.199	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
A/Y	0.833	likely_pathogenic	0.8602	pathogenic	-0.541	Destabilizing	0.996	D	0.841	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.