TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29251	87976;87977;87978	chr2:178557511;178557510;178557509	chr2:179422238;179422237;179422236
N2AB	27610	83053;83054;83055	chr2:178557511;178557510;178557509	chr2:179422238;179422237;179422236
N2A	26683	80272;80273;80274	chr2:178557511;178557510;178557509	chr2:179422238;179422237;179422236
N2B	20186	60781;60782;60783	chr2:178557511;178557510;178557509	chr2:179422238;179422237;179422236
Novex-1	20311	61156;61157;61158	chr2:178557511;178557510;178557509	chr2:179422238;179422237;179422236
Novex-2	20378	61357;61358;61359	chr2:178557511;178557510;178557509	chr2:179422238;179422237;179422236
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGA
• RefSeq wild type template codon: GCT
• Domain: Fn3-101
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4334
• 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
R/Q	rs373830762	None	0.811	N	0.25	0.109	0.110078149338	gnomAD-4.0.0	4.10512E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49711E-06	0	1.65656E-05

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
R/A	0.4888	ambiguous	0.4924	ambiguous	-0.275	Destabilizing	0.97	D	0.529	neutral	None	None	None	None	N
R/C	0.2814	likely_benign	0.2771	benign	-0.231	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
R/D	0.8588	likely_pathogenic	0.8478	pathogenic	-0.078	Destabilizing	0.991	D	0.571	neutral	None	None	None	None	N
R/E	0.5306	ambiguous	0.5127	ambiguous	-0.003	Destabilizing	0.942	D	0.479	neutral	None	None	None	None	N
R/F	0.8378	likely_pathogenic	0.822	pathogenic	-0.388	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
R/G	0.3279	likely_benign	0.3253	benign	-0.514	Destabilizing	0.992	D	0.587	neutral	N	0.446559988	None	None	N
R/H	0.1694	likely_benign	0.1625	benign	-0.96	Destabilizing	0.996	D	0.453	neutral	None	None	None	None	N
R/I	0.6741	likely_pathogenic	0.6456	pathogenic	0.334	Stabilizing	0.996	D	0.674	neutral	None	None	None	None	N
R/K	0.1292	likely_benign	0.1188	benign	-0.323	Destabilizing	0.155	N	0.089	neutral	None	None	None	None	N
R/L	0.4884	ambiguous	0.4897	ambiguous	0.334	Stabilizing	0.984	D	0.587	neutral	N	0.512419621	None	None	N
R/M	0.5415	ambiguous	0.5206	ambiguous	0.036	Stabilizing	1.0	D	0.544	neutral	None	None	None	None	N
R/N	0.73	likely_pathogenic	0.7226	pathogenic	0.122	Stabilizing	0.97	D	0.478	neutral	None	None	None	None	N
R/P	0.6969	likely_pathogenic	0.6685	pathogenic	0.152	Stabilizing	0.998	D	0.631	neutral	N	0.458257062	None	None	N
R/Q	0.1255	likely_benign	0.1205	benign	-0.063	Destabilizing	0.811	D	0.25	neutral	N	0.482443431	None	None	N
R/S	0.5897	likely_pathogenic	0.5867	pathogenic	-0.395	Destabilizing	0.97	D	0.527	neutral	None	None	None	None	N
R/T	0.4701	ambiguous	0.459	ambiguous	-0.172	Destabilizing	0.985	D	0.549	neutral	None	None	None	None	N
R/V	0.6738	likely_pathogenic	0.6552	pathogenic	0.152	Stabilizing	0.996	D	0.619	neutral	None	None	None	None	N
R/W	0.332	likely_benign	0.324	benign	-0.28	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
R/Y	0.6447	likely_pathogenic	0.6286	pathogenic	0.088	Stabilizing	0.999	D	0.656	neutral	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.