TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28312	85159;85160;85161	chr2:178561198;178561197;178561196	chr2:179425925;179425924;179425923
N2AB	26671	80236;80237;80238	chr2:178561198;178561197;178561196	chr2:179425925;179425924;179425923
N2A	25744	77455;77456;77457	chr2:178561198;178561197;178561196	chr2:179425925;179425924;179425923
N2B	19247	57964;57965;57966	chr2:178561198;178561197;178561196	chr2:179425925;179425924;179425923
Novex-1	19372	58339;58340;58341	chr2:178561198;178561197;178561196	chr2:179425925;179425924;179425923
Novex-2	19439	58540;58541;58542	chr2:178561198;178561197;178561196	chr2:179425925;179425924;179425923
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-94
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.1861
• 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
F/C	rs1703534719	None	0.997	N	0.755	0.419	0.668570387503	gnomAD-4.0.0	1.59178E-06	None	None	None	None	N	None	0	2.28697E-05	None	0	0	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
F/A	0.9322	likely_pathogenic	0.9339	pathogenic	-2.146	Highly Destabilizing	0.86	D	0.571	neutral	None	None	None	None	N
F/C	0.7241	likely_pathogenic	0.7418	pathogenic	-1.273	Destabilizing	0.997	D	0.755	deleterious	N	0.519559024	None	None	N
F/D	0.9892	likely_pathogenic	0.9884	pathogenic	-2.423	Highly Destabilizing	0.978	D	0.749	deleterious	None	None	None	None	N
F/E	0.9883	likely_pathogenic	0.9882	pathogenic	-2.238	Highly Destabilizing	0.956	D	0.741	deleterious	None	None	None	None	N
F/G	0.969	likely_pathogenic	0.9696	pathogenic	-2.541	Highly Destabilizing	0.956	D	0.683	prob.neutral	None	None	None	None	N
F/H	0.84	likely_pathogenic	0.8497	pathogenic	-1.014	Destabilizing	0.978	D	0.654	neutral	None	None	None	None	N
F/I	0.8052	likely_pathogenic	0.789	pathogenic	-0.888	Destabilizing	0.97	D	0.46	neutral	N	0.478041055	None	None	N
F/K	0.9828	likely_pathogenic	0.9831	pathogenic	-1.758	Destabilizing	0.956	D	0.743	deleterious	None	None	None	None	N
F/L	0.9667	likely_pathogenic	0.9705	pathogenic	-0.888	Destabilizing	0.822	D	0.457	neutral	N	0.507781806	None	None	N
F/M	0.845	likely_pathogenic	0.8612	pathogenic	-0.576	Destabilizing	0.998	D	0.486	neutral	None	None	None	None	N
F/N	0.9713	likely_pathogenic	0.971	pathogenic	-2.257	Highly Destabilizing	0.978	D	0.794	deleterious	None	None	None	None	N
F/P	0.9995	likely_pathogenic	0.9995	pathogenic	-1.313	Destabilizing	0.019	N	0.595	neutral	None	None	None	None	N
F/Q	0.9668	likely_pathogenic	0.969	pathogenic	-2.183	Highly Destabilizing	0.978	D	0.803	deleterious	None	None	None	None	N
F/R	0.952	likely_pathogenic	0.9545	pathogenic	-1.346	Destabilizing	0.978	D	0.793	deleterious	None	None	None	None	N
F/S	0.905	likely_pathogenic	0.9046	pathogenic	-2.836	Highly Destabilizing	0.942	D	0.629	neutral	N	0.496767648	None	None	N
F/T	0.9332	likely_pathogenic	0.93	pathogenic	-2.543	Highly Destabilizing	0.956	D	0.627	neutral	None	None	None	None	N
F/V	0.7298	likely_pathogenic	0.7209	pathogenic	-1.313	Destabilizing	0.904	D	0.523	neutral	N	0.466539257	None	None	N
F/W	0.7084	likely_pathogenic	0.7303	pathogenic	-0.13	Destabilizing	0.998	D	0.497	neutral	None	None	None	None	N
F/Y	0.2157	likely_benign	0.2091	benign	-0.401	Destabilizing	0.058	N	0.392	neutral	N	0.4598145	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.