TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29863	89812;89813;89814	chr2:178553313;178553312;178553311	chr2:179418040;179418039;179418038
N2AB	28222	84889;84890;84891	chr2:178553313;178553312;178553311	chr2:179418040;179418039;179418038
N2A	27295	82108;82109;82110	chr2:178553313;178553312;178553311	chr2:179418040;179418039;179418038
N2B	20798	62617;62618;62619	chr2:178553313;178553312;178553311	chr2:179418040;179418039;179418038
Novex-1	20923	62992;62993;62994	chr2:178553313;178553312;178553311	chr2:179418040;179418039;179418038
Novex-2	20990	63193;63194;63195	chr2:178553313;178553312;178553311	chr2:179418040;179418039;179418038
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-147
• Domain position: 22
• Structural Position: 35
• Q(SASA): 0.1433
• 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
F/S	None	None	0.998	N	0.805	0.6	0.746065682744	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
F/A	0.9575	likely_pathogenic	0.9531	pathogenic	-2.332	Highly Destabilizing	0.985	D	0.729	prob.delet.	None	None	None	None	N
F/C	0.6744	likely_pathogenic	0.6507	pathogenic	-1.486	Destabilizing	1.0	D	0.805	deleterious	N	0.492213696	None	None	N
F/D	0.998	likely_pathogenic	0.9976	pathogenic	-0.935	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
F/E	0.9963	likely_pathogenic	0.9957	pathogenic	-0.815	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
F/G	0.9864	likely_pathogenic	0.9849	pathogenic	-2.7	Highly Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
F/H	0.9521	likely_pathogenic	0.9502	pathogenic	-0.979	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
F/I	0.4391	ambiguous	0.4129	ambiguous	-1.21	Destabilizing	0.835	D	0.659	neutral	N	0.398161114	None	None	N
F/K	0.9915	likely_pathogenic	0.9913	pathogenic	-1.421	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
F/L	0.9257	likely_pathogenic	0.9172	pathogenic	-1.21	Destabilizing	0.031	N	0.283	neutral	N	0.468775992	None	None	N
F/M	0.7721	likely_pathogenic	0.7644	pathogenic	-1.0	Destabilizing	0.991	D	0.734	prob.delet.	None	None	None	None	N
F/N	0.9883	likely_pathogenic	0.9878	pathogenic	-1.52	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
F/P	0.9987	likely_pathogenic	0.9984	pathogenic	-1.58	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
F/Q	0.9855	likely_pathogenic	0.9847	pathogenic	-1.543	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
F/R	0.9791	likely_pathogenic	0.9783	pathogenic	-0.811	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
F/S	0.9616	likely_pathogenic	0.9551	pathogenic	-2.405	Highly Destabilizing	0.998	D	0.805	deleterious	N	0.510393328	None	None	N
F/T	0.9637	likely_pathogenic	0.9613	pathogenic	-2.185	Highly Destabilizing	0.985	D	0.796	deleterious	None	None	None	None	N
F/V	0.4615	ambiguous	0.4325	ambiguous	-1.58	Destabilizing	0.835	D	0.686	prob.neutral	N	0.379913709	None	None	N
F/W	0.7653	likely_pathogenic	0.7479	pathogenic	-0.323	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
F/Y	0.3176	likely_benign	0.3032	benign	-0.578	Destabilizing	0.993	D	0.652	neutral	N	0.505448868	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.