TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24943	75052;75053;75054	chr2:178571305;178571304;178571303	chr2:179436032;179436031;179436030
N2AB	23302	70129;70130;70131	chr2:178571305;178571304;178571303	chr2:179436032;179436031;179436030
N2A	22375	67348;67349;67350	chr2:178571305;178571304;178571303	chr2:179436032;179436031;179436030
N2B	15878	47857;47858;47859	chr2:178571305;178571304;178571303	chr2:179436032;179436031;179436030
Novex-1	16003	48232;48233;48234	chr2:178571305;178571304;178571303	chr2:179436032;179436031;179436030
Novex-2	16070	48433;48434;48435	chr2:178571305;178571304;178571303	chr2:179436032;179436031;179436030
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-69
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0839
• 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	rs1708096253	None	1.0	D	0.873	0.933	0.879769576077	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94099E-04	None	0	0	0	0	0
Y/C	rs1708096253	None	1.0	D	0.873	0.933	0.879769576077	gnomAD-4.0.0	2.56321E-06	None	None	None	None	N	None	0	0	None	0	2.42813E-05	None	0	0	2.39398E-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	0.9984	likely_pathogenic	0.9981	pathogenic	-3.639	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/C	0.926	likely_pathogenic	0.9107	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.651191036	None	None	N
Y/D	0.9988	likely_pathogenic	0.9987	pathogenic	-3.74	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.667412201	None	None	N
Y/E	0.9996	likely_pathogenic	0.9995	pathogenic	-3.55	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/F	0.1972	likely_benign	0.1845	benign	-1.391	Destabilizing	0.999	D	0.654	neutral	D	0.578110967	None	None	N
Y/G	0.9942	likely_pathogenic	0.9936	pathogenic	-3.992	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
Y/H	0.9807	likely_pathogenic	0.9778	pathogenic	-2.552	Highly Destabilizing	1.0	D	0.796	deleterious	D	0.650787427	None	None	N
Y/I	0.9844	likely_pathogenic	0.9809	pathogenic	-2.421	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/K	0.999	likely_pathogenic	0.9988	pathogenic	-2.464	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/L	0.9711	likely_pathogenic	0.9689	pathogenic	-2.421	Highly Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
Y/M	0.9903	likely_pathogenic	0.9884	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/N	0.9861	likely_pathogenic	0.9851	pathogenic	-3.123	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.667210397	None	None	N
Y/P	0.9997	likely_pathogenic	0.9997	pathogenic	-2.847	Highly Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	N
Y/Q	0.9989	likely_pathogenic	0.9988	pathogenic	-2.929	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/R	0.996	likely_pathogenic	0.9957	pathogenic	-2.122	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/S	0.9932	likely_pathogenic	0.9924	pathogenic	-3.455	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.667210397	None	None	N
Y/T	0.9982	likely_pathogenic	0.9978	pathogenic	-3.166	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/V	0.9783	likely_pathogenic	0.9736	pathogenic	-2.847	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
Y/W	0.8315	likely_pathogenic	0.8219	pathogenic	-0.611	Destabilizing	1.0	D	0.781	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.