TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27405	82438;82439;82440	chr2:178563919;178563918;178563917	chr2:179428646;179428645;179428644
N2AB	25764	77515;77516;77517	chr2:178563919;178563918;178563917	chr2:179428646;179428645;179428644
N2A	24837	74734;74735;74736	chr2:178563919;178563918;178563917	chr2:179428646;179428645;179428644
N2B	18340	55243;55244;55245	chr2:178563919;178563918;178563917	chr2:179428646;179428645;179428644
Novex-1	18465	55618;55619;55620	chr2:178563919;178563918;178563917	chr2:179428646;179428645;179428644
Novex-2	18532	55819;55820;55821	chr2:178563919;178563918;178563917	chr2:179428646;179428645;179428644
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: Fn3-87
• Domain position: 37
• Structural Position: 38
• Q(SASA): 0.1073
• 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	None	None	0.999	D	0.822	0.787	0.871621880514	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/N	None	None	0.935	D	0.84	0.844	0.889760517707	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9946	likely_pathogenic	0.9944	pathogenic	-3.662	Highly Destabilizing	0.916	D	0.786	deleterious	None	None	None	None	N
Y/C	0.8565	likely_pathogenic	0.8424	pathogenic	-1.912	Destabilizing	0.999	D	0.822	deleterious	D	0.663263597	None	None	N
Y/D	0.9942	likely_pathogenic	0.9946	pathogenic	-3.839	Highly Destabilizing	0.025	N	0.726	prob.delet.	D	0.663465402	None	None	N
Y/E	0.9987	likely_pathogenic	0.9987	pathogenic	-3.636	Highly Destabilizing	0.845	D	0.789	deleterious	None	None	None	None	N
Y/F	0.2036	likely_benign	0.2024	benign	-1.736	Destabilizing	0.981	D	0.636	neutral	D	0.546768739	None	None	N
Y/G	0.9848	likely_pathogenic	0.9835	pathogenic	-4.024	Highly Destabilizing	0.975	D	0.809	deleterious	None	None	None	None	N
Y/H	0.9538	likely_pathogenic	0.9504	pathogenic	-2.848	Highly Destabilizing	0.994	D	0.713	prob.delet.	D	0.637321877	None	None	N
Y/I	0.9695	likely_pathogenic	0.9662	pathogenic	-2.412	Highly Destabilizing	0.987	D	0.772	deleterious	None	None	None	None	N
Y/K	0.9978	likely_pathogenic	0.9979	pathogenic	-2.722	Highly Destabilizing	0.975	D	0.836	deleterious	None	None	None	None	N
Y/L	0.9355	likely_pathogenic	0.9294	pathogenic	-2.412	Highly Destabilizing	0.957	D	0.736	prob.delet.	None	None	None	None	N
Y/M	0.9815	likely_pathogenic	0.9796	pathogenic	-2.032	Highly Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
Y/N	0.9697	likely_pathogenic	0.9663	pathogenic	-3.467	Highly Destabilizing	0.935	D	0.84	deleterious	D	0.663263597	None	None	N
Y/P	0.9988	likely_pathogenic	0.9988	pathogenic	-2.85	Highly Destabilizing	0.987	D	0.88	deleterious	None	None	None	None	N
Y/Q	0.9968	likely_pathogenic	0.9967	pathogenic	-3.21	Highly Destabilizing	0.987	D	0.77	deleterious	None	None	None	None	N
Y/R	0.9904	likely_pathogenic	0.9907	pathogenic	-2.497	Highly Destabilizing	0.987	D	0.85	deleterious	None	None	None	None	N
Y/S	0.9782	likely_pathogenic	0.9773	pathogenic	-3.713	Highly Destabilizing	0.967	D	0.776	deleterious	D	0.663263597	None	None	N
Y/T	0.9927	likely_pathogenic	0.9921	pathogenic	-3.405	Highly Destabilizing	0.975	D	0.816	deleterious	None	None	None	None	N
Y/V	0.9465	likely_pathogenic	0.9403	pathogenic	-2.85	Highly Destabilizing	0.987	D	0.729	prob.delet.	None	None	None	None	N
Y/W	0.8425	likely_pathogenic	0.8379	pathogenic	-0.986	Destabilizing	0.999	D	0.704	prob.neutral	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.