TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26306	79141;79142;79143	chr2:178567216;178567215;178567214	chr2:179431943;179431942;179431941
N2AB	24665	74218;74219;74220	chr2:178567216;178567215;178567214	chr2:179431943;179431942;179431941
N2A	23738	71437;71438;71439	chr2:178567216;178567215;178567214	chr2:179431943;179431942;179431941
N2B	17241	51946;51947;51948	chr2:178567216;178567215;178567214	chr2:179431943;179431942;179431941
Novex-1	17366	52321;52322;52323	chr2:178567216;178567215;178567214	chr2:179431943;179431942;179431941
Novex-2	17433	52522;52523;52524	chr2:178567216;178567215;178567214	chr2:179431943;179431942;179431941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-79
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.0888
• 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/S	rs374124734	None	0.994	D	0.911	0.653	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/S	rs374124734	None	0.994	D	0.911	0.653	None	gnomAD-4.0.0	6.57445E-06	None	None	None	None	N	None	2.41348E-05	0	None	0	0	None	0	0	0	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	0.9496	likely_pathogenic	0.9617	pathogenic	-2.444	Highly Destabilizing	0.968	D	0.75	deleterious	None	None	None	None	N
L/C	0.8855	likely_pathogenic	0.9166	pathogenic	-2.01	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-2.811	Highly Destabilizing	0.998	D	0.928	deleterious	None	None	None	None	N
L/E	0.9984	likely_pathogenic	0.9987	pathogenic	-2.494	Highly Destabilizing	0.998	D	0.917	deleterious	None	None	None	None	N
L/F	0.5637	ambiguous	0.6687	pathogenic	-1.478	Destabilizing	0.988	D	0.736	prob.delet.	N	0.514797722	None	None	N
L/G	0.9954	likely_pathogenic	0.9967	pathogenic	-3.077	Highly Destabilizing	0.995	D	0.914	deleterious	None	None	None	None	N
L/H	0.9955	likely_pathogenic	0.9968	pathogenic	-2.827	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/I	0.086	likely_benign	0.083	benign	-0.568	Destabilizing	0.067	N	0.333	neutral	N	0.514505495	None	None	N
L/K	0.9973	likely_pathogenic	0.9978	pathogenic	-1.793	Destabilizing	0.995	D	0.909	deleterious	None	None	None	None	N
L/M	0.2857	likely_benign	0.3282	benign	-0.846	Destabilizing	0.991	D	0.725	prob.delet.	None	None	None	None	N
L/N	0.9987	likely_pathogenic	0.9989	pathogenic	-2.399	Highly Destabilizing	0.998	D	0.937	deleterious	None	None	None	None	N
L/P	0.998	likely_pathogenic	0.9979	pathogenic	-1.179	Destabilizing	0.998	D	0.937	deleterious	None	None	None	None	N
L/Q	0.9937	likely_pathogenic	0.9952	pathogenic	-2.051	Highly Destabilizing	1.0	D	0.941	deleterious	None	None	None	None	N
L/R	0.9942	likely_pathogenic	0.995	pathogenic	-1.904	Destabilizing	0.998	D	0.932	deleterious	None	None	None	None	N
L/S	0.9957	likely_pathogenic	0.997	pathogenic	-3.105	Highly Destabilizing	0.994	D	0.911	deleterious	D	0.565275826	None	None	N
L/T	0.9718	likely_pathogenic	0.9781	pathogenic	-2.605	Highly Destabilizing	0.991	D	0.815	deleterious	None	None	None	None	N
L/V	0.1045	likely_benign	0.1095	benign	-1.179	Destabilizing	0.618	D	0.672	neutral	D	0.522506116	None	None	N
L/W	0.9804	likely_pathogenic	0.9881	pathogenic	-1.868	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/Y	0.982	likely_pathogenic	0.9883	pathogenic	-1.571	Destabilizing	0.995	D	0.842	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.