TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32488	97687;97688;97689	chr2:178542294;178542293;178542292	chr2:179407021;179407020;179407019
N2AB	30847	92764;92765;92766	chr2:178542294;178542293;178542292	chr2:179407021;179407020;179407019
N2A	29920	89983;89984;89985	chr2:178542294;178542293;178542292	chr2:179407021;179407020;179407019
N2B	23423	70492;70493;70494	chr2:178542294;178542293;178542292	chr2:179407021;179407020;179407019
Novex-1	23548	70867;70868;70869	chr2:178542294;178542293;178542292	chr2:179407021;179407020;179407019
Novex-2	23615	71068;71069;71070	chr2:178542294;178542293;178542292	chr2:179407021;179407020;179407019
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-124
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.101
• 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
S/F	None	None	0.999	N	0.839	0.447	0.743508982932	gnomAD-4.0.0	1.23355E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.62055E-05	0	0
S/P	None	None	0.999	N	0.789	0.483	0.360565625551	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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
S/A	0.4984	ambiguous	0.4586	ambiguous	-0.343	Destabilizing	0.994	D	0.659	prob.neutral	N	0.491536955	None	None	N
S/C	0.5926	likely_pathogenic	0.5358	ambiguous	-0.182	Destabilizing	1.0	D	0.75	deleterious	N	0.518163586	None	None	N
S/D	0.9596	likely_pathogenic	0.9531	pathogenic	-0.291	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	N
S/E	0.987	likely_pathogenic	0.9862	pathogenic	-0.151	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	N
S/F	0.9875	likely_pathogenic	0.9825	pathogenic	-0.294	Destabilizing	0.999	D	0.839	deleterious	N	0.517656607	None	None	N
S/G	0.3931	ambiguous	0.3322	benign	-0.707	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	N
S/H	0.9789	likely_pathogenic	0.9741	pathogenic	-1.05	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
S/I	0.971	likely_pathogenic	0.9671	pathogenic	0.55	Stabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
S/K	0.9977	likely_pathogenic	0.9973	pathogenic	0.007	Stabilizing	0.998	D	0.594	neutral	None	None	None	None	N
S/L	0.8349	likely_pathogenic	0.8064	pathogenic	0.55	Stabilizing	0.999	D	0.696	prob.delet.	None	None	None	None	N
S/M	0.839	likely_pathogenic	0.8272	pathogenic	0.327	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
S/N	0.8876	likely_pathogenic	0.8606	pathogenic	-0.457	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
S/P	0.9909	likely_pathogenic	0.9894	pathogenic	0.289	Stabilizing	0.999	D	0.789	deleterious	N	0.499552352	None	None	N
S/Q	0.9862	likely_pathogenic	0.9844	pathogenic	-0.274	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
S/R	0.9976	likely_pathogenic	0.9968	pathogenic	-0.291	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
S/T	0.2157	likely_benign	0.1845	benign	-0.253	Destabilizing	0.997	D	0.613	neutral	D	0.522559257	None	None	N
S/V	0.9331	likely_pathogenic	0.9215	pathogenic	0.289	Stabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
S/W	0.9827	likely_pathogenic	0.978	pathogenic	-0.505	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
S/Y	0.9742	likely_pathogenic	0.966	pathogenic	-0.037	Destabilizing	0.999	D	0.854	deleterious	D	0.529012912	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.