TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32972	99139;99140;99141	chr2:178539021;178539020;178539019	chr2:179403748;179403747;179403746
N2AB	31331	94216;94217;94218	chr2:178539021;178539020;178539019	chr2:179403748;179403747;179403746
N2A	30404	91435;91436;91437	chr2:178539021;178539020;178539019	chr2:179403748;179403747;179403746
N2B	23907	71944;71945;71946	chr2:178539021;178539020;178539019	chr2:179403748;179403747;179403746
Novex-1	24032	72319;72320;72321	chr2:178539021;178539020;178539019	chr2:179403748;179403747;179403746
Novex-2	24099	72520;72521;72522	chr2:178539021;178539020;178539019	chr2:179403748;179403747;179403746
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-128
• Domain position: 77
• Structural Position: 108
• Q(SASA): 0.0703
• 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
I/T	None	None	0.896	D	0.531	0.448	0.706878895572	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85871E-06	0	0
I/V	None	None	0.004	N	0.23	0.082	0.167679373172	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79902E-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
I/A	0.9484	likely_pathogenic	0.9262	pathogenic	-2.886	Highly Destabilizing	0.702	D	0.579	neutral	None	None	None	None	N
I/C	0.9484	likely_pathogenic	0.9313	pathogenic	-2.246	Highly Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
I/D	0.999	likely_pathogenic	0.9981	pathogenic	-3.645	Highly Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
I/E	0.9973	likely_pathogenic	0.9956	pathogenic	-3.355	Highly Destabilizing	0.988	D	0.824	deleterious	None	None	None	None	N
I/F	0.8384	likely_pathogenic	0.7948	pathogenic	-1.577	Destabilizing	0.968	D	0.675	neutral	N	0.479516448	None	None	N
I/G	0.9929	likely_pathogenic	0.987	pathogenic	-3.46	Highly Destabilizing	0.988	D	0.793	deleterious	None	None	None	None	N
I/H	0.9976	likely_pathogenic	0.9959	pathogenic	-3.038	Highly Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
I/K	0.9965	likely_pathogenic	0.9944	pathogenic	-2.225	Highly Destabilizing	0.988	D	0.829	deleterious	None	None	None	None	N
I/L	0.4379	ambiguous	0.4107	ambiguous	-1.166	Destabilizing	0.437	N	0.341	neutral	N	0.462340304	None	None	N
I/M	0.4613	ambiguous	0.4058	ambiguous	-1.406	Destabilizing	0.984	D	0.669	neutral	N	0.500034688	None	None	N
I/N	0.9823	likely_pathogenic	0.9697	pathogenic	-2.822	Highly Destabilizing	0.995	D	0.851	deleterious	N	0.498381172	None	None	N
I/P	0.9959	likely_pathogenic	0.9944	pathogenic	-1.729	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
I/Q	0.9958	likely_pathogenic	0.9931	pathogenic	-2.545	Highly Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
I/R	0.9943	likely_pathogenic	0.9909	pathogenic	-2.101	Highly Destabilizing	0.988	D	0.855	deleterious	None	None	None	None	N
I/S	0.9737	likely_pathogenic	0.955	pathogenic	-3.394	Highly Destabilizing	0.984	D	0.754	deleterious	N	0.487024866	None	None	N
I/T	0.9464	likely_pathogenic	0.9227	pathogenic	-2.958	Highly Destabilizing	0.896	D	0.531	neutral	D	0.527952008	None	None	N
I/V	0.0983	likely_benign	0.0855	benign	-1.729	Destabilizing	0.004	N	0.23	neutral	N	0.326003787	None	None	N
I/W	0.9979	likely_pathogenic	0.9964	pathogenic	-2.046	Highly Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
I/Y	0.9868	likely_pathogenic	0.9812	pathogenic	-1.856	Destabilizing	0.988	D	0.725	prob.delet.	None	None	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.