TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26446	79561;79562;79563	chr2:178566796;178566795;178566794	chr2:179431523;179431522;179431521
N2AB	24805	74638;74639;74640	chr2:178566796;178566795;178566794	chr2:179431523;179431522;179431521
N2A	23878	71857;71858;71859	chr2:178566796;178566795;178566794	chr2:179431523;179431522;179431521
N2B	17381	52366;52367;52368	chr2:178566796;178566795;178566794	chr2:179431523;179431522;179431521
Novex-1	17506	52741;52742;52743	chr2:178566796;178566795;178566794	chr2:179431523;179431522;179431521
Novex-2	17573	52942;52943;52944	chr2:178566796;178566795;178566794	chr2:179431523;179431522;179431521
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-80
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.2235
• 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/I	None	None	0.811	N	0.52	0.091	0.165133752707	gnomAD-4.0.0	6.84399E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15942E-05	0
L/V	None	None	0.896	N	0.521	0.087	0.165133752707	gnomAD-4.0.0	6.84399E-07	None	None	None	None	N	None	0	0	None	0	2.5227E-05	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	0.6096	likely_pathogenic	0.64	pathogenic	-1.889	Destabilizing	0.959	D	0.535	neutral	None	None	None	None	N
L/C	0.4417	ambiguous	0.4783	ambiguous	-1.266	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
L/D	0.9708	likely_pathogenic	0.9795	pathogenic	-1.682	Destabilizing	0.996	D	0.789	deleterious	None	None	None	None	N
L/E	0.8331	likely_pathogenic	0.8724	pathogenic	-1.532	Destabilizing	0.996	D	0.761	deleterious	None	None	None	None	N
L/F	0.0957	likely_benign	0.101	benign	-1.045	Destabilizing	0.015	N	0.267	neutral	None	None	None	None	N
L/G	0.8336	likely_pathogenic	0.8602	pathogenic	-2.351	Highly Destabilizing	0.988	D	0.723	prob.delet.	None	None	None	None	N
L/H	0.4355	ambiguous	0.4729	ambiguous	-1.588	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
L/I	0.148	likely_benign	0.1487	benign	-0.617	Destabilizing	0.811	D	0.52	neutral	N	0.491372345	None	None	N
L/K	0.7861	likely_pathogenic	0.8212	pathogenic	-1.526	Destabilizing	0.996	D	0.69	prob.neutral	None	None	None	None	N
L/M	0.1142	likely_benign	0.1111	benign	-0.541	Destabilizing	0.988	D	0.566	neutral	None	None	None	None	N
L/N	0.7973	likely_pathogenic	0.8099	pathogenic	-1.717	Destabilizing	0.996	D	0.8	deleterious	None	None	None	None	N
L/P	0.9854	likely_pathogenic	0.9915	pathogenic	-1.014	Destabilizing	0.995	D	0.803	deleterious	N	0.500908705	None	None	N
L/Q	0.3757	ambiguous	0.4287	ambiguous	-1.661	Destabilizing	0.995	D	0.745	deleterious	N	0.474157169	None	None	N
L/R	0.68	likely_pathogenic	0.7402	pathogenic	-1.139	Destabilizing	0.995	D	0.727	prob.delet.	N	0.48904542	None	None	N
L/S	0.6988	likely_pathogenic	0.7113	pathogenic	-2.389	Highly Destabilizing	0.988	D	0.623	neutral	None	None	None	None	N
L/T	0.6214	likely_pathogenic	0.6396	pathogenic	-2.097	Highly Destabilizing	0.988	D	0.605	neutral	None	None	None	None	N
L/V	0.143	likely_benign	0.1481	benign	-1.014	Destabilizing	0.896	D	0.521	neutral	N	0.460622577	None	None	N
L/W	0.315	likely_benign	0.3687	ambiguous	-1.312	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
L/Y	0.2665	likely_benign	0.2846	benign	-1.008	Destabilizing	0.851	D	0.565	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.