TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31362	94309;94310;94311	chr2:178547542;178547541;178547540	chr2:179412269;179412268;179412267
N2AB	29721	89386;89387;89388	chr2:178547542;178547541;178547540	chr2:179412269;179412268;179412267
N2A	28794	86605;86606;86607	chr2:178547542;178547541;178547540	chr2:179412269;179412268;179412267
N2B	22297	67114;67115;67116	chr2:178547542;178547541;178547540	chr2:179412269;179412268;179412267
Novex-1	22422	67489;67490;67491	chr2:178547542;178547541;178547540	chr2:179412269;179412268;179412267
Novex-2	22489	67690;67691;67692	chr2:178547542;178547541;178547540	chr2:179412269;179412268;179412267
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-116
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.6102
• 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
S/G	None	None	0.999	N	0.554	0.292	0.243398259712	gnomAD-4.0.0	3.42112E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.4973E-06	0	0
S/R	None	None	1.0	N	0.787	0.511	0.318252033908	gnomAD-4.0.0	6.84218E-07	None	None	None	None	I	None	0	2.23654E-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
S/A	0.1472	likely_benign	0.1159	benign	-0.471	Destabilizing	0.998	D	0.445	neutral	None	None	None	None	I
S/C	0.2564	likely_benign	0.1833	benign	-0.286	Destabilizing	1.0	D	0.74	deleterious	N	0.49385804	None	None	I
S/D	0.954	likely_pathogenic	0.9301	pathogenic	-0.123	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
S/E	0.9675	likely_pathogenic	0.9483	pathogenic	-0.221	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
S/F	0.7675	likely_pathogenic	0.6535	pathogenic	-1.073	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
S/G	0.2937	likely_benign	0.2134	benign	-0.58	Destabilizing	0.999	D	0.554	neutral	N	0.474192094	None	None	I
S/H	0.8725	likely_pathogenic	0.8056	pathogenic	-1.112	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
S/I	0.7615	likely_pathogenic	0.6598	pathogenic	-0.312	Destabilizing	1.0	D	0.798	deleterious	N	0.49385804	None	None	I
S/K	0.9898	likely_pathogenic	0.9815	pathogenic	-0.563	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	I
S/L	0.3607	ambiguous	0.2785	benign	-0.312	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
S/M	0.5172	ambiguous	0.4302	ambiguous	0.085	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
S/N	0.6518	likely_pathogenic	0.5686	pathogenic	-0.299	Destabilizing	0.999	D	0.647	neutral	N	0.499223824	None	None	I
S/P	0.9669	likely_pathogenic	0.9328	pathogenic	-0.337	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
S/Q	0.9175	likely_pathogenic	0.877	pathogenic	-0.609	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
S/R	0.9776	likely_pathogenic	0.9607	pathogenic	-0.295	Destabilizing	1.0	D	0.787	deleterious	N	0.496087519	None	None	I
S/T	0.2183	likely_benign	0.1668	benign	-0.403	Destabilizing	0.999	D	0.532	neutral	N	0.454816899	None	None	I
S/V	0.6366	likely_pathogenic	0.5144	ambiguous	-0.337	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
S/W	0.8782	likely_pathogenic	0.8129	pathogenic	-1.053	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
S/Y	0.7409	likely_pathogenic	0.6298	pathogenic	-0.79	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.