TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30981	93166;93167;93168	chr2:178548685;178548684;178548683	chr2:179413412;179413411;179413410
N2AB	29340	88243;88244;88245	chr2:178548685;178548684;178548683	chr2:179413412;179413411;179413410
N2A	28413	85462;85463;85464	chr2:178548685;178548684;178548683	chr2:179413412;179413411;179413410
N2B	21916	65971;65972;65973	chr2:178548685;178548684;178548683	chr2:179413412;179413411;179413410
Novex-1	22041	66346;66347;66348	chr2:178548685;178548684;178548683	chr2:179413412;179413411;179413410
Novex-2	22108	66547;66548;66549	chr2:178548685;178548684;178548683	chr2:179413412;179413411;179413410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-150
• Domain position: 55
• Structural Position: 138
• Q(SASA): 0.1326
• 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/P	None	None	1.0	D	0.847	0.86	0.912582988975	gnomAD-4.0.0	7.52609E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.89403E-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	0.9295	likely_pathogenic	0.922	pathogenic	-2.484	Highly Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
L/C	0.9061	likely_pathogenic	0.894	pathogenic	-1.841	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.281	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/E	0.9978	likely_pathogenic	0.9974	pathogenic	-2.945	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/F	0.5879	likely_pathogenic	0.5876	pathogenic	-1.495	Destabilizing	1.0	D	0.783	deleterious	N	0.497504659	None	None	N
L/G	0.9939	likely_pathogenic	0.9922	pathogenic	-3.105	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
L/H	0.9926	likely_pathogenic	0.9903	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.821	deleterious	D	0.546603638	None	None	N
L/I	0.1955	likely_benign	0.2097	benign	-0.61	Destabilizing	0.999	D	0.636	neutral	N	0.51278453	None	None	N
L/K	0.9954	likely_pathogenic	0.9946	pathogenic	-1.875	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/M	0.2679	likely_benign	0.2758	benign	-0.918	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/N	0.9981	likely_pathogenic	0.9974	pathogenic	-2.643	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/P	0.999	likely_pathogenic	0.9984	pathogenic	-1.227	Destabilizing	1.0	D	0.847	deleterious	D	0.558124527	None	None	N
L/Q	0.9887	likely_pathogenic	0.9863	pathogenic	-2.228	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/R	0.9901	likely_pathogenic	0.9883	pathogenic	-2.116	Highly Destabilizing	1.0	D	0.846	deleterious	D	0.558124527	None	None	N
L/S	0.9947	likely_pathogenic	0.9932	pathogenic	-3.159	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/T	0.9812	likely_pathogenic	0.9764	pathogenic	-2.647	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/V	0.1969	likely_benign	0.2163	benign	-1.227	Destabilizing	0.999	D	0.638	neutral	N	0.50697486	None	None	N
L/W	0.9762	likely_pathogenic	0.9734	pathogenic	-1.91	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
L/Y	0.9625	likely_pathogenic	0.9599	pathogenic	-1.686	Destabilizing	1.0	D	0.809	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.