TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20346	61261;61262;61263	chr2:178590689;178590688;178590687	chr2:179455416;179455415;179455414
N2AB	18705	56338;56339;56340	chr2:178590689;178590688;178590687	chr2:179455416;179455415;179455414
N2A	17778	53557;53558;53559	chr2:178590689;178590688;178590687	chr2:179455416;179455415;179455414
N2B	11281	34066;34067;34068	chr2:178590689;178590688;178590687	chr2:179455416;179455415;179455414
Novex-1	11406	34441;34442;34443	chr2:178590689;178590688;178590687	chr2:179455416;179455415;179455414
Novex-2	11473	34642;34643;34644	chr2:178590689;178590688;178590687	chr2:179455416;179455415;179455414
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: Fn3-35
• Domain position: 76
• Structural Position: 109
• Q(SASA): 0.0947
• 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/S	rs2050017310	None	0.971	N	0.683	0.481	0.465549362696	gnomAD-4.0.0	4.77807E-06	None	None	None	None	N	None	0	0	None	0	8.33936E-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
F/A	0.6436	likely_pathogenic	0.7073	pathogenic	-3.33	Highly Destabilizing	0.86	D	0.61	neutral	None	None	None	None	N
F/C	0.3994	ambiguous	0.4806	ambiguous	-1.871	Destabilizing	0.997	D	0.724	prob.delet.	N	0.474170664	None	None	N
F/D	0.9509	likely_pathogenic	0.9618	pathogenic	-3.332	Highly Destabilizing	0.993	D	0.767	deleterious	None	None	None	None	N
F/E	0.9455	likely_pathogenic	0.96	pathogenic	-3.18	Highly Destabilizing	0.978	D	0.768	deleterious	None	None	None	None	N
F/G	0.9039	likely_pathogenic	0.9213	pathogenic	-3.706	Highly Destabilizing	0.978	D	0.722	prob.delet.	None	None	None	None	N
F/H	0.6826	likely_pathogenic	0.7349	pathogenic	-1.96	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
F/I	0.3132	likely_benign	0.4168	ambiguous	-2.099	Highly Destabilizing	0.698	D	0.619	neutral	N	0.452024523	None	None	N
F/K	0.9456	likely_pathogenic	0.9536	pathogenic	-2.185	Highly Destabilizing	0.978	D	0.753	deleterious	None	None	None	None	N
F/L	0.8758	likely_pathogenic	0.9235	pathogenic	-2.099	Highly Destabilizing	0.014	N	0.437	neutral	N	0.487675892	None	None	N
F/M	0.5078	ambiguous	0.6142	pathogenic	-1.675	Destabilizing	0.956	D	0.713	prob.delet.	None	None	None	None	N
F/N	0.8132	likely_pathogenic	0.8564	pathogenic	-2.442	Highly Destabilizing	0.993	D	0.781	deleterious	None	None	None	None	N
F/P	0.999	likely_pathogenic	0.9993	pathogenic	-2.52	Highly Destabilizing	0.993	D	0.775	deleterious	None	None	None	None	N
F/Q	0.8801	likely_pathogenic	0.9062	pathogenic	-2.547	Highly Destabilizing	0.993	D	0.775	deleterious	None	None	None	None	N
F/R	0.8777	likely_pathogenic	0.8897	pathogenic	-1.405	Destabilizing	0.978	D	0.781	deleterious	None	None	None	None	N
F/S	0.4571	ambiguous	0.5095	ambiguous	-3.094	Highly Destabilizing	0.971	D	0.683	prob.neutral	N	0.439634016	None	None	N
F/T	0.4966	ambiguous	0.588	pathogenic	-2.855	Highly Destabilizing	0.956	D	0.668	neutral	None	None	None	None	N
F/V	0.3193	likely_benign	0.414	ambiguous	-2.52	Highly Destabilizing	0.698	D	0.593	neutral	N	0.46982085	None	None	N
F/W	0.5689	likely_pathogenic	0.6071	pathogenic	-0.807	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
F/Y	0.1774	likely_benign	0.1943	benign	-1.235	Destabilizing	0.904	D	0.617	neutral	N	0.45787306	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.