TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22252	66979;66980;66981	chr2:178581514;178581513;178581512	chr2:179446241;179446240;179446239
N2AB	20611	62056;62057;62058	chr2:178581514;178581513;178581512	chr2:179446241;179446240;179446239
N2A	19684	59275;59276;59277	chr2:178581514;178581513;178581512	chr2:179446241;179446240;179446239
N2B	13187	39784;39785;39786	chr2:178581514;178581513;178581512	chr2:179446241;179446240;179446239
Novex-1	13312	40159;40160;40161	chr2:178581514;178581513;178581512	chr2:179446241;179446240;179446239
Novex-2	13379	40360;40361;40362	chr2:178581514;178581513;178581512	chr2:179446241;179446240;179446239
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-49
• Domain position: 97
• Structural Position: 130
• Q(SASA): 0.0841
• 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/L	None	None	0.799	N	0.755	0.329	0.574126200305	gnomAD-4.0.0	1.62684E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.07844E-05

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	0.1426	likely_benign	0.1585	benign	-2.008	Highly Destabilizing	0.002	N	0.441	neutral	N	0.399411907	None	None	N
P/C	0.6902	likely_pathogenic	0.7048	pathogenic	-2.399	Highly Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
P/D	0.9974	likely_pathogenic	0.9973	pathogenic	-3.038	Highly Destabilizing	0.974	D	0.685	prob.delet.	None	None	None	None	N
P/E	0.9884	likely_pathogenic	0.9884	pathogenic	-2.909	Highly Destabilizing	0.841	D	0.688	prob.delet.	None	None	None	None	N
P/F	0.9912	likely_pathogenic	0.9889	pathogenic	-1.383	Destabilizing	0.974	D	0.777	deleterious	None	None	None	None	N
P/G	0.8515	likely_pathogenic	0.867	pathogenic	-2.407	Highly Destabilizing	0.725	D	0.663	prob.neutral	None	None	None	None	N
P/H	0.9871	likely_pathogenic	0.9857	pathogenic	-1.869	Destabilizing	0.997	D	0.758	deleterious	N	0.48386545	None	None	N
P/I	0.7831	likely_pathogenic	0.7431	pathogenic	-0.93	Destabilizing	0.949	D	0.767	deleterious	None	None	None	None	N
P/K	0.9929	likely_pathogenic	0.9924	pathogenic	-1.744	Destabilizing	0.841	D	0.683	prob.neutral	None	None	None	None	N
P/L	0.6348	likely_pathogenic	0.6109	pathogenic	-0.93	Destabilizing	0.799	D	0.755	deleterious	N	0.516833724	None	None	N
P/M	0.8814	likely_pathogenic	0.8642	pathogenic	-1.33	Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	N
P/N	0.9866	likely_pathogenic	0.985	pathogenic	-2.045	Highly Destabilizing	0.974	D	0.763	deleterious	None	None	None	None	N
P/Q	0.9609	likely_pathogenic	0.959	pathogenic	-2.092	Highly Destabilizing	0.974	D	0.735	deleterious	None	None	None	None	N
P/R	0.9733	likely_pathogenic	0.9733	pathogenic	-1.38	Destabilizing	0.966	D	0.759	deleterious	N	0.49487936	None	None	N
P/S	0.6916	likely_pathogenic	0.6995	pathogenic	-2.577	Highly Destabilizing	0.666	D	0.637	neutral	N	0.482598002	None	None	N
P/T	0.5361	ambiguous	0.5299	ambiguous	-2.324	Highly Destabilizing	0.799	D	0.654	prob.neutral	N	0.498247963	None	None	N
P/V	0.5149	ambiguous	0.4782	ambiguous	-1.263	Destabilizing	0.725	D	0.7	prob.delet.	None	None	None	None	N
P/W	0.9984	likely_pathogenic	0.9983	pathogenic	-1.69	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
P/Y	0.9961	likely_pathogenic	0.9955	pathogenic	-1.377	Destabilizing	0.991	D	0.777	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.