TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4902	14929;14930;14931	chr2:178735742;178735741;178735740	chr2:179600469;179600468;179600467
N2AB	4585	13978;13979;13980	chr2:178735742;178735741;178735740	chr2:179600469;179600468;179600467
N2A	3658	11197;11198;11199	chr2:178735742;178735741;178735740	chr2:179600469;179600468;179600467
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-32
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.5262
• 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
N/H	rs1461011434	None	0.999	D	0.559	0.487	0.371531589858	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/H	rs1461011434	None	0.999	D	0.559	0.487	0.371531589858	gnomAD-4.0.0	6.56996E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46977E-05	0	0
N/S	rs1208544617	None	0.978	D	0.519	0.401	0.29527378943	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs1208544617	None	0.978	D	0.519	0.401	0.29527378943	gnomAD-4.0.0	2.5621E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78572E-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
N/A	0.3887	ambiguous	0.458	ambiguous	-0.268	Destabilizing	0.967	D	0.571	neutral	None	None	None	None	I
N/C	0.4572	ambiguous	0.5204	ambiguous	0.285	Stabilizing	1.0	D	0.616	neutral	None	None	None	None	I
N/D	0.2122	likely_benign	0.2556	benign	0.298	Stabilizing	0.989	D	0.521	neutral	D	0.627470422	None	None	I
N/E	0.572	likely_pathogenic	0.6337	pathogenic	0.283	Stabilizing	0.997	D	0.545	neutral	None	None	None	None	I
N/F	0.6672	likely_pathogenic	0.7228	pathogenic	-0.552	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	I
N/G	0.2221	likely_benign	0.2514	benign	-0.463	Destabilizing	0.071	N	0.293	neutral	None	None	None	None	I
N/H	0.1305	likely_benign	0.1525	benign	-0.396	Destabilizing	0.999	D	0.559	neutral	D	0.680532133	None	None	I
N/I	0.5486	ambiguous	0.6266	pathogenic	0.162	Stabilizing	0.999	D	0.603	neutral	D	0.782756257	None	None	I
N/K	0.4223	ambiguous	0.4717	ambiguous	0.118	Stabilizing	0.997	D	0.541	neutral	D	0.648494355	None	None	I
N/L	0.369	ambiguous	0.4139	ambiguous	0.162	Stabilizing	0.998	D	0.579	neutral	None	None	None	None	I
N/M	0.5079	ambiguous	0.5652	pathogenic	0.318	Stabilizing	1.0	D	0.571	neutral	None	None	None	None	I
N/P	0.734	likely_pathogenic	0.7763	pathogenic	0.046	Stabilizing	0.999	D	0.549	neutral	None	None	None	None	I
N/Q	0.3879	ambiguous	0.4405	ambiguous	-0.293	Destabilizing	0.999	D	0.539	neutral	None	None	None	None	I
N/R	0.4385	ambiguous	0.4846	ambiguous	0.148	Stabilizing	0.999	D	0.53	neutral	None	None	None	None	I
N/S	0.0919	likely_benign	0.1051	benign	-0.159	Destabilizing	0.978	D	0.519	neutral	D	0.591007689	None	None	I
N/T	0.2555	likely_benign	0.3049	benign	-0.022	Destabilizing	0.989	D	0.547	neutral	D	0.672055556	None	None	I
N/V	0.5558	ambiguous	0.6311	pathogenic	0.046	Stabilizing	0.999	D	0.585	neutral	None	None	None	None	I
N/W	0.7903	likely_pathogenic	0.8317	pathogenic	-0.534	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	I
N/Y	0.2319	likely_benign	0.2726	benign	-0.263	Destabilizing	0.999	D	0.565	neutral	D	0.726479198	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.