TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8396	25411;25412;25413	chr2:178717688;178717687;178717686	chr2:179582415;179582414;179582413
N2AB	8079	24460;24461;24462	chr2:178717688;178717687;178717686	chr2:179582415;179582414;179582413
N2A	7152	21679;21680;21681	chr2:178717688;178717687;178717686	chr2:179582415;179582414;179582413
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: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-69
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.6658
• 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/N	rs771290213	-0.271	0.545	N	0.335	0.21	0.0666544352282	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	9.97E-05	0	None	0	None	0	0	0
D/N	rs771290213	-0.271	0.545	N	0.335	0.21	0.0666544352282	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs771290213	-0.271	0.545	N	0.335	0.21	0.0666544352282	gnomAD-4.0.0	2.56338E-06	None	None	None	None	N	None	0	0	None	4.09098E-05	0	None	0	0	2.39403E-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	0.5264	ambiguous	0.6702	pathogenic	-0.56	Destabilizing	0.998	D	0.63	neutral	N	0.478535494	None	None	N
D/C	0.9255	likely_pathogenic	0.9557	pathogenic	-0.154	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
D/E	0.4256	ambiguous	0.5633	ambiguous	-0.379	Destabilizing	0.907	D	0.443	neutral	N	0.449364422	None	None	N
D/F	0.9222	likely_pathogenic	0.9619	pathogenic	-0.183	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
D/G	0.3174	likely_benign	0.4355	ambiguous	-0.826	Destabilizing	0.984	D	0.634	neutral	N	0.452362935	None	None	N
D/H	0.7311	likely_pathogenic	0.8488	pathogenic	-0.117	Destabilizing	1.0	D	0.657	neutral	N	0.490398778	None	None	N
D/I	0.9272	likely_pathogenic	0.9632	pathogenic	0.119	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
D/K	0.8335	likely_pathogenic	0.9171	pathogenic	0.134	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	N
D/L	0.8616	likely_pathogenic	0.9244	pathogenic	0.119	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
D/M	0.9416	likely_pathogenic	0.9674	pathogenic	0.358	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	N
D/N	0.1575	likely_benign	0.1706	benign	-0.388	Destabilizing	0.545	D	0.335	neutral	N	0.454791817	None	None	N
D/P	0.9917	likely_pathogenic	0.9961	pathogenic	-0.084	Destabilizing	0.994	D	0.681	prob.neutral	None	None	None	None	N
D/Q	0.7691	likely_pathogenic	0.8765	pathogenic	-0.301	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
D/R	0.8273	likely_pathogenic	0.9166	pathogenic	0.37	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
D/S	0.3487	ambiguous	0.4462	ambiguous	-0.523	Destabilizing	0.991	D	0.603	neutral	None	None	None	None	N
D/T	0.8078	likely_pathogenic	0.8822	pathogenic	-0.297	Destabilizing	0.994	D	0.675	neutral	None	None	None	None	N
D/V	0.771	likely_pathogenic	0.8744	pathogenic	-0.084	Destabilizing	0.999	D	0.681	prob.neutral	N	0.484068902	None	None	N
D/W	0.977	likely_pathogenic	0.9897	pathogenic	0.078	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
D/Y	0.5471	ambiguous	0.7064	pathogenic	0.089	Stabilizing	1.0	D	0.669	neutral	N	0.513529463	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.