TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30823	92692;92693;92694	chr2:178549159;178549158;178549157	chr2:179413886;179413885;179413884
N2AB	29182	87769;87770;87771	chr2:178549159;178549158;178549157	chr2:179413886;179413885;179413884
N2A	28255	84988;84989;84990	chr2:178549159;178549158;178549157	chr2:179413886;179413885;179413884
N2B	21758	65497;65498;65499	chr2:178549159;178549158;178549157	chr2:179413886;179413885;179413884
Novex-1	21883	65872;65873;65874	chr2:178549159;178549158;178549157	chr2:179413886;179413885;179413884
Novex-2	21950	66073;66074;66075	chr2:178549159;178549158;178549157	chr2:179413886;179413885;179413884
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-113
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.3061
• 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
G/S	rs727504934	-1.093	None	N	0.125	0.143	0.0716867268079	gnomAD-2.1.1	5.22E-05	None	None	None	None	I	None	0	0	None	0	0	None	4.24864E-04	None	0	0	0
G/S	rs727504934	-1.093	None	N	0.125	0.143	0.0716867268079	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	4.14766E-04	0
G/S	rs727504934	-1.093	None	N	0.125	0.143	0.0716867268079	gnomAD-4.0.0	3.03661E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	5.1603E-04	3.20246E-05

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
G/A	0.1063	likely_benign	0.1126	benign	-0.844	Destabilizing	0.012	N	0.311	neutral	N	0.502687498	None	None	I
G/C	0.14	likely_benign	0.1365	benign	-1.139	Destabilizing	0.78	D	0.493	neutral	D	0.53121346	None	None	I
G/D	0.3739	ambiguous	0.4177	ambiguous	-1.85	Destabilizing	0.062	N	0.395	neutral	N	0.462449609	None	None	I
G/E	0.4009	ambiguous	0.4427	ambiguous	-1.878	Destabilizing	0.081	N	0.436	neutral	None	None	None	None	I
G/F	0.5489	ambiguous	0.5749	pathogenic	-1.098	Destabilizing	0.555	D	0.535	neutral	None	None	None	None	I
G/H	0.5185	ambiguous	0.5399	ambiguous	-1.452	Destabilizing	0.824	D	0.438	neutral	None	None	None	None	I
G/I	0.332	likely_benign	0.3511	ambiguous	-0.4	Destabilizing	0.38	N	0.499	neutral	None	None	None	None	I
G/K	0.711	likely_pathogenic	0.7413	pathogenic	-1.323	Destabilizing	0.081	N	0.435	neutral	None	None	None	None	I
G/L	0.3131	likely_benign	0.3397	benign	-0.4	Destabilizing	0.149	N	0.472	neutral	None	None	None	None	I
G/M	0.3985	ambiguous	0.4096	ambiguous	-0.409	Destabilizing	0.935	D	0.493	neutral	None	None	None	None	I
G/N	0.3571	ambiguous	0.3649	ambiguous	-1.126	Destabilizing	0.081	N	0.445	neutral	None	None	None	None	I
G/P	0.8985	likely_pathogenic	0.9103	pathogenic	-0.508	Destabilizing	0.38	N	0.445	neutral	None	None	None	None	I
G/Q	0.5059	ambiguous	0.5348	ambiguous	-1.314	Destabilizing	0.38	N	0.453	neutral	None	None	None	None	I
G/R	0.5747	likely_pathogenic	0.6165	pathogenic	-1.04	Destabilizing	0.317	N	0.44	neutral	N	0.507322307	None	None	I
G/S	0.0788	likely_benign	0.0852	benign	-1.343	Destabilizing	None	N	0.125	neutral	N	0.46190295	None	None	I
G/T	0.1706	likely_benign	0.1711	benign	-1.305	Destabilizing	0.002	N	0.34	neutral	None	None	None	None	I
G/V	0.2479	likely_benign	0.2664	benign	-0.508	Destabilizing	0.117	N	0.469	neutral	N	0.519185592	None	None	I
G/W	0.5364	ambiguous	0.5734	pathogenic	-1.499	Destabilizing	0.935	D	0.495	neutral	None	None	None	None	I
G/Y	0.4475	ambiguous	0.4632	ambiguous	-1.082	Destabilizing	0.555	D	0.515	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.