TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31034	93325;93326;93327	chr2:178548526;178548525;178548524	chr2:179413253;179413252;179413251
N2AB	29393	88402;88403;88404	chr2:178548526;178548525;178548524	chr2:179413253;179413252;179413251
N2A	28466	85621;85622;85623	chr2:178548526;178548525;178548524	chr2:179413253;179413252;179413251
N2B	21969	66130;66131;66132	chr2:178548526;178548525;178548524	chr2:179413253;179413252;179413251
Novex-1	22094	66505;66506;66507	chr2:178548526;178548525;178548524	chr2:179413253;179413252;179413251
Novex-2	22161	66706;66707;66708	chr2:178548526;178548525;178548524	chr2:179413253;179413252;179413251
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-114
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.12
• 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
T/A	rs1575474576	None	0.999	N	0.546	0.496	0.348324211639	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92976E-04	None	0	0	0	0	0
T/A	rs1575474576	None	0.999	N	0.546	0.496	0.348324211639	gnomAD-4.0.0	5.12411E-06	None	None	None	None	N	None	0	0	None	0	9.69697E-05	None	0	0	0	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
T/A	0.1618	likely_benign	0.1515	benign	-1.006	Destabilizing	0.999	D	0.546	neutral	N	0.48039814	None	None	N
T/C	0.5796	likely_pathogenic	0.5774	pathogenic	-0.713	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
T/D	0.9246	likely_pathogenic	0.8863	pathogenic	-1.088	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/E	0.8481	likely_pathogenic	0.8093	pathogenic	-0.938	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
T/F	0.4083	ambiguous	0.3965	ambiguous	-0.644	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
T/G	0.5756	likely_pathogenic	0.5161	ambiguous	-1.402	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/H	0.5841	likely_pathogenic	0.5448	ambiguous	-1.606	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
T/I	0.2201	likely_benign	0.212	benign	0.013	Stabilizing	1.0	D	0.775	deleterious	N	0.519887098	None	None	N
T/K	0.7513	likely_pathogenic	0.7151	pathogenic	-0.735	Destabilizing	1.0	D	0.753	deleterious	N	0.470282829	None	None	N
T/L	0.1471	likely_benign	0.1474	benign	0.013	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	N
T/M	0.1123	likely_benign	0.1178	benign	0.071	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
T/N	0.3905	ambiguous	0.3502	ambiguous	-1.189	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
T/P	0.777	likely_pathogenic	0.737	pathogenic	-0.293	Destabilizing	1.0	D	0.789	deleterious	D	0.526761641	None	None	N
T/Q	0.5825	likely_pathogenic	0.5606	ambiguous	-1.046	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
T/R	0.6703	likely_pathogenic	0.6285	pathogenic	-0.847	Destabilizing	1.0	D	0.795	deleterious	N	0.482853675	None	None	N
T/S	0.2152	likely_benign	0.1923	benign	-1.415	Destabilizing	0.999	D	0.535	neutral	N	0.485734452	None	None	N
T/V	0.1325	likely_benign	0.1381	benign	-0.293	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
T/W	0.8066	likely_pathogenic	0.8044	pathogenic	-0.757	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/Y	0.5214	ambiguous	0.4891	ambiguous	-0.429	Destabilizing	1.0	D	0.841	deleterious	None	None	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.