TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28764	86515;86516;86517	chr2:178559842;178559841;178559840	chr2:179424569;179424568;179424567
N2AB	27123	81592;81593;81594	chr2:178559842;178559841;178559840	chr2:179424569;179424568;179424567
N2A	26196	78811;78812;78813	chr2:178559842;178559841;178559840	chr2:179424569;179424568;179424567
N2B	19699	59320;59321;59322	chr2:178559842;178559841;178559840	chr2:179424569;179424568;179424567
Novex-1	19824	59695;59696;59697	chr2:178559842;178559841;178559840	chr2:179424569;179424568;179424567
Novex-2	19891	59896;59897;59898	chr2:178559842;178559841;178559840	chr2:179424569;179424568;179424567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-144
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.1517
• 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
L/V	None	None	0.63	N	0.51	0.117	0.324986149311	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
L/A	0.5604	ambiguous	0.5337	ambiguous	-1.853	Destabilizing	0.916	D	0.569	neutral	None	None	None	None	N
L/C	0.6501	likely_pathogenic	0.6477	pathogenic	-1.234	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
L/D	0.9531	likely_pathogenic	0.9504	pathogenic	-1.441	Destabilizing	0.975	D	0.766	deleterious	None	None	None	None	N
L/E	0.7464	likely_pathogenic	0.7356	pathogenic	-1.349	Destabilizing	0.975	D	0.768	deleterious	None	None	None	None	N
L/F	0.2198	likely_benign	0.2047	benign	-1.131	Destabilizing	0.983	D	0.627	neutral	N	0.487342306	None	None	N
L/G	0.9054	likely_pathogenic	0.8947	pathogenic	-2.253	Highly Destabilizing	0.975	D	0.767	deleterious	None	None	None	None	N
L/H	0.4205	ambiguous	0.4112	ambiguous	-1.344	Destabilizing	0.154	N	0.556	neutral	None	None	None	None	N
L/I	0.1037	likely_benign	0.0961	benign	-0.784	Destabilizing	0.253	N	0.366	neutral	None	None	None	None	N
L/K	0.5344	ambiguous	0.5384	ambiguous	-1.386	Destabilizing	0.975	D	0.72	prob.delet.	None	None	None	None	N
L/M	0.1234	likely_benign	0.1214	benign	-0.716	Destabilizing	0.983	D	0.64	neutral	N	0.485189485	None	None	N
L/N	0.7669	likely_pathogenic	0.7573	pathogenic	-1.423	Destabilizing	0.975	D	0.774	deleterious	None	None	None	None	N
L/P	0.9643	likely_pathogenic	0.9547	pathogenic	-1.113	Destabilizing	0.996	D	0.776	deleterious	None	None	None	None	N
L/Q	0.334	likely_benign	0.3311	benign	-1.464	Destabilizing	0.975	D	0.717	prob.delet.	None	None	None	None	N
L/R	0.422	ambiguous	0.4266	ambiguous	-0.882	Destabilizing	0.975	D	0.717	prob.delet.	None	None	None	None	N
L/S	0.7086	likely_pathogenic	0.6828	pathogenic	-2.07	Highly Destabilizing	0.967	D	0.687	prob.neutral	N	0.505193071	None	None	N
L/T	0.5159	ambiguous	0.4965	ambiguous	-1.84	Destabilizing	0.987	D	0.658	neutral	None	None	None	None	N
L/V	0.1015	likely_benign	0.0992	benign	-1.113	Destabilizing	0.63	D	0.51	neutral	N	0.473795023	None	None	N
L/W	0.4804	ambiguous	0.4733	ambiguous	-1.266	Destabilizing	0.999	D	0.691	prob.neutral	D	0.524818263	None	None	N
L/Y	0.526	ambiguous	0.5133	ambiguous	-1.023	Destabilizing	0.95	D	0.691	prob.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.