TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15735	47428;47429;47430	chr2:178618255;178618254;178618253	chr2:179482982;179482981;179482980
N2AB	14094	42505;42506;42507	chr2:178618255;178618254;178618253	chr2:179482982;179482981;179482980
N2A	13167	39724;39725;39726	chr2:178618255;178618254;178618253	chr2:179482982;179482981;179482980
N2B	6670	20233;20234;20235	chr2:178618255;178618254;178618253	chr2:179482982;179482981;179482980
Novex-1	6795	20608;20609;20610	chr2:178618255;178618254;178618253	chr2:179482982;179482981;179482980
Novex-2	6862	20809;20810;20811	chr2:178618255;178618254;178618253	chr2:179482982;179482981;179482980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-1
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.4013
• Predicted PPI site: I

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
R/G	rs780694414	-1.931	0.722	N	0.669	0.231	0.411401001288	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
R/G	rs780694414	-1.931	0.722	N	0.669	0.231	0.411401001288	gnomAD-4.0.0	1.59317E-06	None	None	None	None	I	None	0	0	None	0	2.77701E-05	None	0	0	0	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
R/A	0.6926	likely_pathogenic	0.7246	pathogenic	-1.583	Destabilizing	0.633	D	0.567	neutral	None	None	None	None	I
R/C	0.3278	likely_benign	0.3032	benign	-1.702	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	I
R/D	0.9441	likely_pathogenic	0.958	pathogenic	-0.641	Destabilizing	0.923	D	0.713	prob.delet.	None	None	None	None	I
R/E	0.5566	ambiguous	0.5823	pathogenic	-0.514	Destabilizing	0.633	D	0.487	neutral	None	None	None	None	I
R/F	0.7836	likely_pathogenic	0.7673	pathogenic	-1.45	Destabilizing	0.987	D	0.768	deleterious	None	None	None	None	I
R/G	0.6698	likely_pathogenic	0.7245	pathogenic	-1.874	Destabilizing	0.722	D	0.669	neutral	N	0.47655721	None	None	I
R/H	0.2227	likely_benign	0.2439	benign	-1.849	Destabilizing	0.961	D	0.589	neutral	None	None	None	None	I
R/I	0.3933	ambiguous	0.3702	ambiguous	-0.78	Destabilizing	0.949	D	0.778	deleterious	N	0.464257781	None	None	I
R/K	0.1023	likely_benign	0.111	benign	-1.604	Destabilizing	0.003	N	0.214	neutral	N	0.452873891	None	None	I
R/L	0.472	ambiguous	0.477	ambiguous	-0.78	Destabilizing	0.775	D	0.669	neutral	None	None	None	None	I
R/M	0.4178	ambiguous	0.4277	ambiguous	-1.008	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	I
R/N	0.8591	likely_pathogenic	0.8768	pathogenic	-1.047	Destabilizing	0.923	D	0.609	neutral	None	None	None	None	I
R/P	0.9858	likely_pathogenic	0.9878	pathogenic	-1.031	Destabilizing	0.961	D	0.786	deleterious	None	None	None	None	I
R/Q	0.1305	likely_benign	0.1376	benign	-1.277	Destabilizing	0.858	D	0.624	neutral	None	None	None	None	I
R/S	0.7691	likely_pathogenic	0.8043	pathogenic	-1.981	Destabilizing	0.565	D	0.626	neutral	N	0.483496696	None	None	I
R/T	0.4176	ambiguous	0.4201	ambiguous	-1.677	Destabilizing	0.722	D	0.676	prob.neutral	N	0.477258131	None	None	I
R/V	0.4364	ambiguous	0.4315	ambiguous	-1.031	Destabilizing	0.923	D	0.769	deleterious	None	None	None	None	I
R/W	0.3916	ambiguous	0.422	ambiguous	-0.972	Destabilizing	0.996	D	0.69	prob.neutral	None	None	None	None	I
R/Y	0.6741	likely_pathogenic	0.6851	pathogenic	-0.713	Destabilizing	0.987	D	0.773	deleterious	None	None	None	None	I

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.