TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8679	26260;26261;26262	chr2:178715151;178715150;178715149	chr2:179579878;179579877;179579876
N2AB	8362	25309;25310;25311	chr2:178715151;178715150;178715149	chr2:179579878;179579877;179579876
N2A	7435	22528;22529;22530	chr2:178715151;178715150;178715149	chr2:179579878;179579877;179579876
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-72
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.592
• 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
D/A	rs373587266	None	0.999	N	0.59	0.453	0.37262878642	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/A	rs373587266	None	0.999	N	0.59	0.453	0.37262878642	gnomAD-4.0.0	6.56564E-06	None	None	None	None	N	None	2.40535E-05	0	None	0	0	None	0	0	0	0	0
D/V	None	None	1.0	N	0.697	0.468	0.549460442827	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85876E-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
D/A	0.461	ambiguous	0.5664	pathogenic	-0.062	Destabilizing	0.999	D	0.59	neutral	N	0.480791944	None	None	N
D/C	0.8788	likely_pathogenic	0.9147	pathogenic	0.03	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
D/E	0.2415	likely_benign	0.2916	benign	-0.242	Destabilizing	0.946	D	0.413	neutral	N	0.510757822	None	None	N
D/F	0.8448	likely_pathogenic	0.8917	pathogenic	-0.121	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
D/G	0.1902	likely_benign	0.2389	benign	-0.219	Destabilizing	0.991	D	0.549	neutral	N	0.461518692	None	None	N
D/H	0.6724	likely_pathogenic	0.7528	pathogenic	0.197	Stabilizing	1.0	D	0.616	neutral	N	0.505986543	None	None	N
D/I	0.8285	likely_pathogenic	0.8898	pathogenic	0.29	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
D/K	0.775	likely_pathogenic	0.8428	pathogenic	0.386	Stabilizing	1.0	D	0.585	neutral	None	None	None	None	N
D/L	0.7454	likely_pathogenic	0.8077	pathogenic	0.29	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
D/M	0.885	likely_pathogenic	0.9184	pathogenic	0.242	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
D/N	0.156	likely_benign	0.1975	benign	0.202	Stabilizing	0.483	N	0.293	neutral	N	0.476967748	None	None	N
D/P	0.979	likely_pathogenic	0.9845	pathogenic	0.194	Stabilizing	0.997	D	0.624	neutral	None	None	None	None	N
D/Q	0.6548	likely_pathogenic	0.734	pathogenic	0.212	Stabilizing	0.999	D	0.565	neutral	None	None	None	None	N
D/R	0.7922	likely_pathogenic	0.8529	pathogenic	0.56	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
D/S	0.3191	likely_benign	0.4101	ambiguous	0.09	Stabilizing	0.995	D	0.507	neutral	None	None	None	None	N
D/T	0.7147	likely_pathogenic	0.7926	pathogenic	0.208	Stabilizing	0.997	D	0.579	neutral	None	None	None	None	N
D/V	0.6381	likely_pathogenic	0.734	pathogenic	0.194	Stabilizing	1.0	D	0.697	prob.neutral	N	0.47826073	None	None	N
D/W	0.9589	likely_pathogenic	0.9724	pathogenic	-0.06	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
D/Y	0.4462	ambiguous	0.5517	ambiguous	0.104	Stabilizing	1.0	D	0.681	prob.neutral	N	0.517760922	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.