TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16686	50281;50282;50283	chr2:178612469;178612468;178612467	chr2:179477196;179477195;179477194
N2AB	15045	45358;45359;45360	chr2:178612469;178612468;178612467	chr2:179477196;179477195;179477194
N2A	14118	42577;42578;42579	chr2:178612469;178612468;178612467	chr2:179477196;179477195;179477194
N2B	7621	23086;23087;23088	chr2:178612469;178612468;178612467	chr2:179477196;179477195;179477194
Novex-1	7746	23461;23462;23463	chr2:178612469;178612468;178612467	chr2:179477196;179477195;179477194
Novex-2	7813	23662;23663;23664	chr2:178612469;178612468;178612467	chr2:179477196;179477195;179477194
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: Fn3-9
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1035
• 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/C	rs2056512518	-2.208	1.0	D	0.887	0.962	0.897505141811	Peled (2013)	None	RCM	het	None	None	N	Segregation analysis in single RCM family, co-segregates with phenotype (n = 5, 5 affected (total 13))	None	None	None	None	None	None	None	None	None	None	None

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	0.9984	likely_pathogenic	0.9992	pathogenic	-3.693	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/C	0.9745	likely_pathogenic	0.9853	pathogenic	-2.147	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.837928079	None	None	N
Y/D	0.9983	likely_pathogenic	0.9994	pathogenic	-3.998	Highly Destabilizing	1.0	D	0.922	deleterious	D	0.837555981	None	None	N
Y/E	0.9996	likely_pathogenic	0.9998	pathogenic	-3.785	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
Y/F	0.4012	ambiguous	0.4421	ambiguous	-1.526	Destabilizing	0.999	D	0.63	neutral	D	0.593177948	None	None	N
Y/G	0.9942	likely_pathogenic	0.9969	pathogenic	-4.097	Highly Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
Y/H	0.9912	likely_pathogenic	0.9959	pathogenic	-2.761	Highly Destabilizing	1.0	D	0.802	deleterious	D	0.785571782	None	None	N
Y/I	0.985	likely_pathogenic	0.9892	pathogenic	-2.319	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/K	0.9994	likely_pathogenic	0.9997	pathogenic	-2.638	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/L	0.9576	likely_pathogenic	0.9681	pathogenic	-2.319	Highly Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
Y/M	0.9924	likely_pathogenic	0.9953	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/N	0.9905	likely_pathogenic	0.996	pathogenic	-3.436	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.837928079	None	None	N
Y/P	0.9995	likely_pathogenic	0.9997	pathogenic	-2.798	Highly Destabilizing	1.0	D	0.949	deleterious	None	None	None	None	N
Y/Q	0.9994	likely_pathogenic	0.9997	pathogenic	-3.177	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
Y/R	0.9972	likely_pathogenic	0.9984	pathogenic	-2.353	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/S	0.9942	likely_pathogenic	0.9974	pathogenic	-3.743	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.837928079	None	None	N
Y/T	0.997	likely_pathogenic	0.9986	pathogenic	-3.413	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
Y/V	0.9736	likely_pathogenic	0.9807	pathogenic	-2.798	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/W	0.9158	likely_pathogenic	0.9294	pathogenic	-0.767	Destabilizing	1.0	D	0.792	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.