TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17564	52915;52916;52917	chr2:178608193;178608192;178608191	chr2:179472920;179472919;179472918
N2AB	15923	47992;47993;47994	chr2:178608193;178608192;178608191	chr2:179472920;179472919;179472918
N2A	14996	45211;45212;45213	chr2:178608193;178608192;178608191	chr2:179472920;179472919;179472918
N2B	8499	25720;25721;25722	chr2:178608193;178608192;178608191	chr2:179472920;179472919;179472918
Novex-1	8624	26095;26096;26097	chr2:178608193;178608192;178608191	chr2:179472920;179472919;179472918
Novex-2	8691	26296;26297;26298	chr2:178608193;178608192;178608191	chr2:179472920;179472919;179472918
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-15
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.0815
• 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
A/V	None	None	0.015	N	0.347	0.279	0.214338557667	gnomAD-4.0.0	1.62001E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.90476E-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
A/C	0.5819	likely_pathogenic	0.6497	pathogenic	-2.032	Highly Destabilizing	0.996	D	0.701	prob.delet.	None	None	None	None	N
A/D	0.9978	likely_pathogenic	0.9982	pathogenic	-3.206	Highly Destabilizing	0.953	D	0.757	deleterious	None	None	None	None	N
A/E	0.9949	likely_pathogenic	0.9965	pathogenic	-3.113	Highly Destabilizing	0.938	D	0.693	prob.delet.	N	0.485143129	None	None	N
A/F	0.9828	likely_pathogenic	0.9854	pathogenic	-0.919	Destabilizing	0.909	D	0.743	deleterious	None	None	None	None	N
A/G	0.6859	likely_pathogenic	0.6902	pathogenic	-1.282	Destabilizing	0.813	D	0.555	neutral	N	0.466696479	None	None	N
A/H	0.996	likely_pathogenic	0.997	pathogenic	-1.307	Destabilizing	0.996	D	0.76	deleterious	None	None	None	None	N
A/I	0.8801	likely_pathogenic	0.8953	pathogenic	-0.235	Destabilizing	0.329	N	0.649	prob.neutral	None	None	None	None	N
A/K	0.9979	likely_pathogenic	0.9986	pathogenic	-1.388	Destabilizing	0.953	D	0.676	prob.neutral	None	None	None	None	N
A/L	0.8031	likely_pathogenic	0.843	pathogenic	-0.235	Destabilizing	0.587	D	0.604	neutral	None	None	None	None	N
A/M	0.8991	likely_pathogenic	0.924	pathogenic	-0.703	Destabilizing	0.974	D	0.726	deleterious	None	None	None	None	N
A/N	0.9882	likely_pathogenic	0.9899	pathogenic	-1.8	Destabilizing	0.953	D	0.746	deleterious	None	None	None	None	N
A/P	0.9317	likely_pathogenic	0.897	pathogenic	-0.448	Destabilizing	0.979	D	0.715	prob.delet.	N	0.485396618	None	None	N
A/Q	0.9861	likely_pathogenic	0.991	pathogenic	-1.855	Destabilizing	0.984	D	0.683	prob.neutral	None	None	None	None	N
A/R	0.9867	likely_pathogenic	0.9924	pathogenic	-1.172	Destabilizing	0.953	D	0.691	prob.delet.	None	None	None	None	N
A/S	0.4312	ambiguous	0.4553	ambiguous	-2.005	Highly Destabilizing	0.518	D	0.552	neutral	N	0.484889639	None	None	N
A/T	0.734	likely_pathogenic	0.7557	pathogenic	-1.823	Destabilizing	0.062	N	0.341	neutral	N	0.466696479	None	None	N
A/V	0.6535	likely_pathogenic	0.6852	pathogenic	-0.448	Destabilizing	0.015	N	0.347	neutral	N	0.458374686	None	None	N
A/W	0.9986	likely_pathogenic	0.9991	pathogenic	-1.47	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
A/Y	0.9942	likely_pathogenic	0.9956	pathogenic	-1.002	Destabilizing	0.953	D	0.745	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.