TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4827	14704;14705;14706	chr2:178735967;178735966;178735965	chr2:179600694;179600693;179600692
N2AB	4510	13753;13754;13755	chr2:178735967;178735966;178735965	chr2:179600694;179600693;179600692
N2A	3583	10972;10973;10974	chr2:178735967;178735966;178735965	chr2:179600694;179600693;179600692
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-31
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.4956
• 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
I/N	None	None	0.655	N	0.603	0.263	0.767856249327	gnomAD-4.0.0	6.84205E-07	None	None	None	None	I	None	0	0	None	0	2.52042E-05	None	0	0	0	0	0
I/T	None	None	0.003	N	0.278	0.205	0.583677480531	gnomAD-4.0.0	6.84205E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99457E-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
I/A	0.3056	likely_benign	0.2121	benign	-1.281	Destabilizing	0.001	N	0.291	neutral	None	None	None	None	I
I/C	0.7089	likely_pathogenic	0.5913	pathogenic	-0.52	Destabilizing	0.94	D	0.545	neutral	None	None	None	None	I
I/D	0.6721	likely_pathogenic	0.5203	ambiguous	-0.858	Destabilizing	0.418	N	0.591	neutral	None	None	None	None	I
I/E	0.5035	ambiguous	0.394	ambiguous	-0.913	Destabilizing	0.418	N	0.559	neutral	None	None	None	None	I
I/F	0.1904	likely_benign	0.1376	benign	-1.067	Destabilizing	0.351	N	0.517	neutral	N	0.50845784	None	None	I
I/G	0.6333	likely_pathogenic	0.4818	ambiguous	-1.541	Destabilizing	0.264	N	0.528	neutral	None	None	None	None	I
I/H	0.447	ambiguous	0.3416	ambiguous	-0.833	Destabilizing	0.983	D	0.529	neutral	None	None	None	None	I
I/K	0.3505	ambiguous	0.2601	benign	-0.742	Destabilizing	0.418	N	0.559	neutral	None	None	None	None	I
I/L	0.1299	likely_benign	0.1089	benign	-0.669	Destabilizing	0.021	N	0.319	neutral	N	0.499318899	None	None	I
I/M	0.1282	likely_benign	0.1061	benign	-0.387	Destabilizing	0.655	D	0.527	neutral	N	0.505400675	None	None	I
I/N	0.2391	likely_benign	0.178	benign	-0.397	Destabilizing	0.655	D	0.603	neutral	N	0.507612107	None	None	I
I/P	0.9434	likely_pathogenic	0.9004	pathogenic	-0.84	Destabilizing	0.593	D	0.612	neutral	None	None	None	None	I
I/Q	0.3945	ambiguous	0.3016	benign	-0.653	Destabilizing	0.836	D	0.562	neutral	None	None	None	None	I
I/R	0.2506	likely_benign	0.1845	benign	-0.112	Destabilizing	0.836	D	0.591	neutral	None	None	None	None	I
I/S	0.2358	likely_benign	0.1761	benign	-0.898	Destabilizing	0.101	N	0.499	neutral	N	0.471788824	None	None	I
I/T	0.1845	likely_benign	0.1391	benign	-0.846	Destabilizing	0.003	N	0.278	neutral	N	0.455487255	None	None	I
I/V	0.0766	likely_benign	0.0667	benign	-0.84	Destabilizing	None	N	0.185	neutral	N	0.485126855	None	None	I
I/W	0.8169	likely_pathogenic	0.7265	pathogenic	-1.109	Destabilizing	0.983	D	0.559	neutral	None	None	None	None	I
I/Y	0.5127	ambiguous	0.408	ambiguous	-0.885	Destabilizing	0.836	D	0.595	neutral	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.