TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32933	99022;99023;99024	chr2:178539138;178539137;178539136	chr2:179403865;179403864;179403863
N2AB	31292	94099;94100;94101	chr2:178539138;178539137;178539136	chr2:179403865;179403864;179403863
N2A	30365	91318;91319;91320	chr2:178539138;178539137;178539136	chr2:179403865;179403864;179403863
N2B	23868	71827;71828;71829	chr2:178539138;178539137;178539136	chr2:179403865;179403864;179403863
Novex-1	23993	72202;72203;72204	chr2:178539138;178539137;178539136	chr2:179403865;179403864;179403863
Novex-2	24060	72403;72404;72405	chr2:178539138;178539137;178539136	chr2:179403865;179403864;179403863
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-128
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.2149
• 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
Y/H	rs775150547	-2.157	1.0	N	0.765	0.368	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	1.24008E-04	0	None	0	0	None	0	None	0	0	0
Y/H	rs775150547	-2.157	1.0	N	0.765	0.368	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20651E-04	0	0	0	0	None	0	0	0	0	0
Y/H	rs775150547	-2.157	1.0	N	0.765	0.368	None	gnomAD-4.0.0	7.68699E-06	None	None	None	None	N	None	1.01492E-04	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
Y/A	0.9092	likely_pathogenic	0.8867	pathogenic	-3.239	Highly Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
Y/C	0.368	ambiguous	0.322	benign	-1.652	Destabilizing	1.0	D	0.781	deleterious	N	0.48188607	None	None	N
Y/D	0.8987	likely_pathogenic	0.8864	pathogenic	-2.728	Highly Destabilizing	1.0	D	0.785	deleterious	N	0.457334342	None	None	N
Y/E	0.9612	likely_pathogenic	0.954	pathogenic	-2.575	Highly Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
Y/F	0.0933	likely_benign	0.0856	benign	-1.309	Destabilizing	0.434	N	0.356	neutral	N	0.427051508	None	None	N
Y/G	0.9446	likely_pathogenic	0.9341	pathogenic	-3.593	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
Y/H	0.3592	ambiguous	0.3643	ambiguous	-1.852	Destabilizing	1.0	D	0.765	deleterious	N	0.442578321	None	None	N
Y/I	0.5967	likely_pathogenic	0.4652	ambiguous	-2.084	Highly Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
Y/K	0.966	likely_pathogenic	0.9556	pathogenic	-1.996	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
Y/L	0.6884	likely_pathogenic	0.6154	pathogenic	-2.084	Highly Destabilizing	0.994	D	0.547	neutral	None	None	None	None	N
Y/M	0.8203	likely_pathogenic	0.7559	pathogenic	-1.737	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
Y/N	0.6385	likely_pathogenic	0.5758	pathogenic	-2.49	Highly Destabilizing	1.0	D	0.785	deleterious	N	0.442980966	None	None	N
Y/P	0.9983	likely_pathogenic	0.998	pathogenic	-2.479	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
Y/Q	0.9004	likely_pathogenic	0.8809	pathogenic	-2.4	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
Y/R	0.8967	likely_pathogenic	0.8814	pathogenic	-1.472	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
Y/S	0.6915	likely_pathogenic	0.6518	pathogenic	-2.951	Highly Destabilizing	1.0	D	0.737	prob.delet.	N	0.44292225	None	None	N
Y/T	0.8322	likely_pathogenic	0.793	pathogenic	-2.703	Highly Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
Y/V	0.5827	likely_pathogenic	0.479	ambiguous	-2.479	Highly Destabilizing	0.997	D	0.648	neutral	None	None	None	None	N
Y/W	0.4688	ambiguous	0.5162	ambiguous	-0.58	Destabilizing	1.0	D	0.747	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.