TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31135	93628;93629;93630	chr2:178548223;178548222;178548221	chr2:179412950;179412949;179412948
N2AB	29494	88705;88706;88707	chr2:178548223;178548222;178548221	chr2:179412950;179412949;179412948
N2A	28567	85924;85925;85926	chr2:178548223;178548222;178548221	chr2:179412950;179412949;179412948
N2B	22070	66433;66434;66435	chr2:178548223;178548222;178548221	chr2:179412950;179412949;179412948
Novex-1	22195	66808;66809;66810	chr2:178548223;178548222;178548221	chr2:179412950;179412949;179412948
Novex-2	22262	67009;67010;67011	chr2:178548223;178548222;178548221	chr2:179412950;179412949;179412948
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-115
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.6508
• 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
L/P	rs1284369744	-1.08	1.0	N	0.823	0.498	0.68219128047	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
L/P	rs1284369744	-1.08	1.0	N	0.823	0.498	0.68219128047	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1284369744	-1.08	1.0	N	0.823	0.498	0.68219128047	gnomAD-4.0.0	2.56197E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78577E-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
L/A	0.2418	likely_benign	0.2751	benign	-2.004	Highly Destabilizing	0.994	D	0.715	prob.delet.	None	None	None	None	I
L/C	0.5245	ambiguous	0.5316	ambiguous	-1.04	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
L/D	0.6484	likely_pathogenic	0.6395	pathogenic	-1.765	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
L/E	0.274	likely_benign	0.2466	benign	-1.7	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
L/F	0.1985	likely_benign	0.2128	benign	-1.297	Destabilizing	0.998	D	0.712	prob.delet.	N	0.515363926	None	None	I
L/G	0.4344	ambiguous	0.4447	ambiguous	-2.385	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	I
L/H	0.2765	likely_benign	0.2684	benign	-1.539	Destabilizing	1.0	D	0.816	deleterious	N	0.496604807	None	None	I
L/I	0.1253	likely_benign	0.1423	benign	-0.989	Destabilizing	0.984	D	0.504	neutral	N	0.460068003	None	None	I
L/K	0.2927	likely_benign	0.253	benign	-1.528	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
L/M	0.0984	likely_benign	0.102	benign	-0.664	Destabilizing	0.971	D	0.39	neutral	None	None	None	None	I
L/N	0.3051	likely_benign	0.3259	benign	-1.44	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
L/P	0.6046	likely_pathogenic	0.6228	pathogenic	-1.3	Destabilizing	1.0	D	0.823	deleterious	N	0.45593162	None	None	I
L/Q	0.1101	likely_benign	0.0997	benign	-1.562	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	I
L/R	0.2731	likely_benign	0.243	benign	-0.884	Destabilizing	0.999	D	0.812	deleterious	N	0.438807297	None	None	I
L/S	0.2399	likely_benign	0.2653	benign	-2.04	Highly Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
L/T	0.1958	likely_benign	0.2157	benign	-1.862	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	I
L/V	0.1058	likely_benign	0.1179	benign	-1.3	Destabilizing	0.984	D	0.528	neutral	N	0.447946855	None	None	I
L/W	0.3778	ambiguous	0.3589	ambiguous	-1.473	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
L/Y	0.4152	ambiguous	0.4214	ambiguous	-1.252	Destabilizing	1.0	D	0.817	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.