TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18201	54826;54827;54828	chr2:178604086;178604085;178604084	chr2:179468813;179468812;179468811
N2AB	16560	49903;49904;49905	chr2:178604086;178604085;178604084	chr2:179468813;179468812;179468811
N2A	15633	47122;47123;47124	chr2:178604086;178604085;178604084	chr2:179468813;179468812;179468811
N2B	9136	27631;27632;27633	chr2:178604086;178604085;178604084	chr2:179468813;179468812;179468811
Novex-1	9261	28006;28007;28008	chr2:178604086;178604085;178604084	chr2:179468813;179468812;179468811
Novex-2	9328	28207;28208;28209	chr2:178604086;178604085;178604084	chr2:179468813;179468812;179468811
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: Fn3-20
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1164
• 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	rs779191742	-2.813	1.0	D	0.835	0.811	0.750328341064	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
Y/H	rs779191742	-2.813	1.0	D	0.835	0.811	0.750328341064	gnomAD-4.0.0	4.77992E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.58821E-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
Y/A	0.997	likely_pathogenic	0.9936	pathogenic	-3.211	Highly Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
Y/C	0.9312	likely_pathogenic	0.8728	pathogenic	-1.736	Destabilizing	1.0	D	0.855	deleterious	D	0.645851249	None	None	N
Y/D	0.9971	likely_pathogenic	0.9958	pathogenic	-3.821	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.646053053	None	None	N
Y/E	0.9989	likely_pathogenic	0.9986	pathogenic	-3.605	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/F	0.2965	likely_benign	0.2523	benign	-1.324	Destabilizing	0.999	D	0.69	prob.neutral	D	0.551644197	None	None	N
Y/G	0.9887	likely_pathogenic	0.983	pathogenic	-3.61	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/H	0.9834	likely_pathogenic	0.9754	pathogenic	-2.455	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.64544764	None	None	N
Y/I	0.9684	likely_pathogenic	0.9514	pathogenic	-1.856	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/K	0.9989	likely_pathogenic	0.9986	pathogenic	-2.465	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/L	0.9455	likely_pathogenic	0.919	pathogenic	-1.856	Destabilizing	0.999	D	0.708	prob.neutral	None	None	None	None	N
Y/M	0.9857	likely_pathogenic	0.9767	pathogenic	-1.551	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
Y/N	0.9813	likely_pathogenic	0.9737	pathogenic	-3.329	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.645851249	None	None	N
Y/P	0.9994	likely_pathogenic	0.9992	pathogenic	-2.327	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/Q	0.9984	likely_pathogenic	0.9974	pathogenic	-3.036	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
Y/R	0.9957	likely_pathogenic	0.9942	pathogenic	-2.339	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/S	0.9873	likely_pathogenic	0.9798	pathogenic	-3.564	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.645851249	None	None	N
Y/T	0.9955	likely_pathogenic	0.9924	pathogenic	-3.228	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/V	0.953	likely_pathogenic	0.9289	pathogenic	-2.327	Highly Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
Y/W	0.8418	likely_pathogenic	0.8286	pathogenic	-0.627	Destabilizing	1.0	D	0.82	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.