TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24640	74143;74144;74145	chr2:178572214;178572213;178572212	chr2:179436941;179436940;179436939
N2AB	22999	69220;69221;69222	chr2:178572214;178572213;178572212	chr2:179436941;179436940;179436939
N2A	22072	66439;66440;66441	chr2:178572214;178572213;178572212	chr2:179436941;179436940;179436939
N2B	15575	46948;46949;46950	chr2:178572214;178572213;178572212	chr2:179436941;179436940;179436939
Novex-1	15700	47323;47324;47325	chr2:178572214;178572213;178572212	chr2:179436941;179436940;179436939
Novex-2	15767	47524;47525;47526	chr2:178572214;178572213;178572212	chr2:179436941;179436940;179436939
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-67
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1191
• 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
P/T	None	None	1.0	D	0.837	0.679	0.608446283964	gnomAD-4.0.0	1.59203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85938E-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
P/A	0.9382	likely_pathogenic	0.9182	pathogenic	-2.038	Highly Destabilizing	1.0	D	0.812	deleterious	D	0.572310441	None	None	N
P/C	0.9971	likely_pathogenic	0.9959	pathogenic	-1.32	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9991	pathogenic	-2.318	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/E	0.9982	likely_pathogenic	0.9978	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9997	pathogenic	-1.438	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
P/G	0.9939	likely_pathogenic	0.9926	pathogenic	-2.454	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/H	0.9986	likely_pathogenic	0.998	pathogenic	-2.098	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/I	0.9974	likely_pathogenic	0.996	pathogenic	-0.933	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/K	0.9992	likely_pathogenic	0.999	pathogenic	-1.825	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/L	0.9865	likely_pathogenic	0.9805	pathogenic	-0.933	Destabilizing	1.0	D	0.878	deleterious	D	0.597444944	None	None	N
P/M	0.9973	likely_pathogenic	0.9961	pathogenic	-0.646	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/N	0.999	likely_pathogenic	0.9987	pathogenic	-1.727	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/Q	0.9979	likely_pathogenic	0.9972	pathogenic	-1.799	Destabilizing	1.0	D	0.82	deleterious	D	0.621206101	None	None	N
P/R	0.9974	likely_pathogenic	0.9967	pathogenic	-1.34	Destabilizing	1.0	D	0.871	deleterious	D	0.588965575	None	None	N
P/S	0.9904	likely_pathogenic	0.9868	pathogenic	-2.259	Highly Destabilizing	1.0	D	0.841	deleterious	D	0.557280459	None	None	N
P/T	0.9863	likely_pathogenic	0.9805	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.837	deleterious	D	0.604783132	None	None	N
P/V	0.9907	likely_pathogenic	0.9864	pathogenic	-1.271	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9998	pathogenic	-1.795	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9996	pathogenic	-1.504	Destabilizing	1.0	D	0.868	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.