TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28497	85714;85715;85716	chr2:178560643;178560642;178560641	chr2:179425370;179425369;179425368
N2AB	26856	80791;80792;80793	chr2:178560643;178560642;178560641	chr2:179425370;179425369;179425368
N2A	25929	78010;78011;78012	chr2:178560643;178560642;178560641	chr2:179425370;179425369;179425368
N2B	19432	58519;58520;58521	chr2:178560643;178560642;178560641	chr2:179425370;179425369;179425368
Novex-1	19557	58894;58895;58896	chr2:178560643;178560642;178560641	chr2:179425370;179425369;179425368
Novex-2	19624	59095;59096;59097	chr2:178560643;178560642;178560641	chr2:179425370;179425369;179425368
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-95
• Domain position: 48
• Structural Position: 64
• Q(SASA): 0.3557
• 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
A/P	None	None	0.994	N	0.593	0.324	0.400468435593	gnomAD-4.0.0	6.84286E-07	None	None	None	None	I	None	0	0	None	0	2.52372E-05	None	0	0	0	0	0
A/S	None	None	0.919	N	0.517	0.155	0.227934060464	gnomAD-4.0.0	6.84286E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99468E-07	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
A/C	0.4792	ambiguous	0.5584	ambiguous	-0.453	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
A/D	0.3916	ambiguous	0.525	ambiguous	-0.816	Destabilizing	0.991	D	0.673	neutral	None	None	None	None	I
A/E	0.3219	likely_benign	0.4217	ambiguous	-0.912	Destabilizing	0.988	D	0.583	neutral	N	0.468511341	None	None	I
A/F	0.3728	ambiguous	0.446	ambiguous	-0.954	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	I
A/G	0.1668	likely_benign	0.2014	benign	-0.724	Destabilizing	0.958	D	0.523	neutral	N	0.480229845	None	None	I
A/H	0.4799	ambiguous	0.561	ambiguous	-0.852	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
A/I	0.244	likely_benign	0.2912	benign	-0.359	Destabilizing	0.991	D	0.609	neutral	None	None	None	None	I
A/K	0.475	ambiguous	0.5942	pathogenic	-0.877	Destabilizing	0.991	D	0.591	neutral	None	None	None	None	I
A/L	0.1534	likely_benign	0.1804	benign	-0.359	Destabilizing	0.938	D	0.541	neutral	None	None	None	None	I
A/M	0.2534	likely_benign	0.2842	benign	-0.328	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	I
A/N	0.2711	likely_benign	0.3375	benign	-0.418	Destabilizing	0.991	D	0.666	neutral	None	None	None	None	I
A/P	0.3008	likely_benign	0.4126	ambiguous	-0.395	Destabilizing	0.994	D	0.593	neutral	N	0.514113132	None	None	I
A/Q	0.3364	likely_benign	0.3884	ambiguous	-0.656	Destabilizing	0.995	D	0.633	neutral	None	None	None	None	I
A/R	0.3762	ambiguous	0.4549	ambiguous	-0.445	Destabilizing	0.991	D	0.597	neutral	None	None	None	None	I
A/S	0.0929	likely_benign	0.1048	benign	-0.618	Destabilizing	0.919	D	0.517	neutral	N	0.438689867	None	None	I
A/T	0.0911	likely_benign	0.1052	benign	-0.64	Destabilizing	0.067	N	0.357	neutral	N	0.441674244	None	None	I
A/V	0.125	likely_benign	0.1428	benign	-0.395	Destabilizing	0.919	D	0.527	neutral	N	0.463377667	None	None	I
A/W	0.7458	likely_pathogenic	0.8143	pathogenic	-1.202	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
A/Y	0.4969	ambiguous	0.5849	pathogenic	-0.832	Destabilizing	0.998	D	0.725	prob.delet.	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.