TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29318	88177;88178;88179	chr2:178557310;178557309;178557308	chr2:179422037;179422036;179422035
N2AB	27677	83254;83255;83256	chr2:178557310;178557309;178557308	chr2:179422037;179422036;179422035
N2A	26750	80473;80474;80475	chr2:178557310;178557309;178557308	chr2:179422037;179422036;179422035
N2B	20253	60982;60983;60984	chr2:178557310;178557309;178557308	chr2:179422037;179422036;179422035
Novex-1	20378	61357;61358;61359	chr2:178557310;178557309;178557308	chr2:179422037;179422036;179422035
Novex-2	20445	61558;61559;61560	chr2:178557310;178557309;178557308	chr2:179422037;179422036;179422035
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-101
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.5592
• 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
A/P	None	None	1.0	D	0.821	0.461	0.466740653422	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.7037	likely_pathogenic	0.7108	pathogenic	-0.754	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
A/D	0.9748	likely_pathogenic	0.9805	pathogenic	-0.763	Destabilizing	1.0	D	0.872	deleterious	N	0.498627299	None	None	I
A/E	0.95	likely_pathogenic	0.9549	pathogenic	-0.934	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
A/F	0.8282	likely_pathogenic	0.8423	pathogenic	-0.992	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
A/G	0.459	ambiguous	0.54	ambiguous	-0.259	Destabilizing	1.0	D	0.623	neutral	N	0.483534784	None	None	I
A/H	0.9413	likely_pathogenic	0.9563	pathogenic	-0.246	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
A/I	0.7036	likely_pathogenic	0.6902	pathogenic	-0.425	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
A/K	0.9665	likely_pathogenic	0.9759	pathogenic	-0.572	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
A/L	0.676	likely_pathogenic	0.694	pathogenic	-0.425	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
A/M	0.7254	likely_pathogenic	0.7344	pathogenic	-0.403	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
A/N	0.9157	likely_pathogenic	0.9351	pathogenic	-0.264	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	I
A/P	0.9734	likely_pathogenic	0.9707	pathogenic	-0.338	Destabilizing	1.0	D	0.821	deleterious	D	0.53002687	None	None	I
A/Q	0.8943	likely_pathogenic	0.9195	pathogenic	-0.608	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
A/R	0.9053	likely_pathogenic	0.9268	pathogenic	-0.03	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
A/S	0.2432	likely_benign	0.2666	benign	-0.399	Destabilizing	1.0	D	0.628	neutral	N	0.479637671	None	None	I
A/T	0.5214	ambiguous	0.5036	ambiguous	-0.505	Destabilizing	1.0	D	0.787	deleterious	N	0.517492023	None	None	I
A/V	0.3373	likely_benign	0.33	benign	-0.338	Destabilizing	1.0	D	0.723	prob.delet.	N	0.464916463	None	None	I
A/W	0.9788	likely_pathogenic	0.9816	pathogenic	-1.084	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
A/Y	0.9227	likely_pathogenic	0.9366	pathogenic	-0.75	Destabilizing	1.0	D	0.883	deleterious	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.