TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32083	96472;96473;96474	chr2:178543897;178543896;178543895	chr2:179408624;179408623;179408622
N2AB	30442	91549;91550;91551	chr2:178543897;178543896;178543895	chr2:179408624;179408623;179408622
N2A	29515	88768;88769;88770	chr2:178543897;178543896;178543895	chr2:179408624;179408623;179408622
N2B	23018	69277;69278;69279	chr2:178543897;178543896;178543895	chr2:179408624;179408623;179408622
Novex-1	23143	69652;69653;69654	chr2:178543897;178543896;178543895	chr2:179408624;179408623;179408622
Novex-2	23210	69853;69854;69855	chr2:178543897;178543896;178543895	chr2:179408624;179408623;179408622
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: Ig-153
• Domain position: 67
• Structural Position: 154
• Q(SASA): 0.1541
• 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	rs1695809971	None	1.0	D	0.801	0.817	0.767440773815	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/H	rs1695809971	None	1.0	D	0.801	0.817	0.767440773815	gnomAD-4.0.0	6.57791E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47076E-05	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	0.9993	likely_pathogenic	0.9991	pathogenic	-2.154	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/C	0.9905	likely_pathogenic	0.9871	pathogenic	-1.901	Destabilizing	1.0	D	0.843	deleterious	D	0.65713803	None	None	N
Y/D	0.9987	likely_pathogenic	0.9985	pathogenic	-2.422	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.673157391	None	None	N
Y/E	0.9996	likely_pathogenic	0.9995	pathogenic	-2.173	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/F	0.2946	likely_benign	0.2859	benign	-0.723	Destabilizing	0.999	D	0.71	prob.delet.	D	0.59734135	None	None	N
Y/G	0.9975	likely_pathogenic	0.9971	pathogenic	-2.608	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/H	0.9939	likely_pathogenic	0.9926	pathogenic	-1.922	Destabilizing	1.0	D	0.801	deleterious	D	0.647417475	None	None	N
Y/I	0.9765	likely_pathogenic	0.9726	pathogenic	-0.666	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/K	0.9996	likely_pathogenic	0.9995	pathogenic	-1.95	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/L	0.962	likely_pathogenic	0.9549	pathogenic	-0.666	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
Y/M	0.9911	likely_pathogenic	0.9894	pathogenic	-0.876	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/N	0.9948	likely_pathogenic	0.9937	pathogenic	-2.813	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.673157391	None	None	N
Y/P	0.9997	likely_pathogenic	0.9997	pathogenic	-1.175	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/Q	0.9997	likely_pathogenic	0.9996	pathogenic	-2.324	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/R	0.999	likely_pathogenic	0.9988	pathogenic	-2.252	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/S	0.9983	likely_pathogenic	0.9979	pathogenic	-3.229	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.673157391	None	None	N
Y/T	0.9992	likely_pathogenic	0.999	pathogenic	-2.831	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
Y/V	0.9767	likely_pathogenic	0.9723	pathogenic	-1.175	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
Y/W	0.8841	likely_pathogenic	0.8847	pathogenic	-0.11	Destabilizing	1.0	D	0.797	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.