TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28008	84247;84248;84249	chr2:178562110;178562109;178562108	chr2:179426837;179426836;179426835
N2AB	26367	79324;79325;79326	chr2:178562110;178562109;178562108	chr2:179426837;179426836;179426835
N2A	25440	76543;76544;76545	chr2:178562110;178562109;178562108	chr2:179426837;179426836;179426835
N2B	18943	57052;57053;57054	chr2:178562110;178562109;178562108	chr2:179426837;179426836;179426835
Novex-1	19068	57427;57428;57429	chr2:178562110;178562109;178562108	chr2:179426837;179426836;179426835
Novex-2	19135	57628;57629;57630	chr2:178562110;178562109;178562108	chr2:179426837;179426836;179426835
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-142
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.3083
• 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/K	None	None	0.997	N	0.461	0.372	0.239305524855	gnomAD-4.0.0	1.59261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85982E-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
R/A	0.8808	likely_pathogenic	0.9026	pathogenic	-0.917	Destabilizing	0.999	D	0.495	neutral	None	None	None	None	N
R/C	0.5762	likely_pathogenic	0.6626	pathogenic	-0.874	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/D	0.9466	likely_pathogenic	0.9604	pathogenic	-0.06	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
R/E	0.8487	likely_pathogenic	0.8803	pathogenic	0.054	Stabilizing	0.999	D	0.551	neutral	None	None	None	None	N
R/F	0.9401	likely_pathogenic	0.9528	pathogenic	-0.839	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
R/G	0.8242	likely_pathogenic	0.867	pathogenic	-1.213	Destabilizing	1.0	D	0.679	prob.neutral	N	0.511493498	None	None	N
R/H	0.3121	likely_benign	0.3643	ambiguous	-1.431	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
R/I	0.8393	likely_pathogenic	0.8672	pathogenic	-0.124	Destabilizing	1.0	D	0.757	deleterious	D	0.523863762	None	None	N
R/K	0.3955	ambiguous	0.3917	ambiguous	-0.884	Destabilizing	0.997	D	0.461	neutral	N	0.475459118	None	None	N
R/L	0.7751	likely_pathogenic	0.8008	pathogenic	-0.124	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
R/M	0.8479	likely_pathogenic	0.8721	pathogenic	-0.382	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
R/N	0.9044	likely_pathogenic	0.9287	pathogenic	-0.312	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
R/P	0.9748	likely_pathogenic	0.9813	pathogenic	-0.368	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
R/Q	0.3748	ambiguous	0.4104	ambiguous	-0.532	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
R/S	0.9088	likely_pathogenic	0.9288	pathogenic	-1.148	Destabilizing	1.0	D	0.693	prob.neutral	N	0.488869793	None	None	N
R/T	0.7908	likely_pathogenic	0.8407	pathogenic	-0.856	Destabilizing	1.0	D	0.694	prob.neutral	N	0.500226098	None	None	N
R/V	0.872	likely_pathogenic	0.8966	pathogenic	-0.368	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
R/W	0.5563	ambiguous	0.6095	pathogenic	-0.475	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
R/Y	0.8182	likely_pathogenic	0.8527	pathogenic	-0.177	Destabilizing	1.0	D	0.725	prob.delet.	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.