TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8201	24826;24827;24828	chr2:178718505;178718504;178718503	chr2:179583232;179583231;179583230
N2AB	7884	23875;23876;23877	chr2:178718505;178718504;178718503	chr2:179583232;179583231;179583230
N2A	6957	21094;21095;21096	chr2:178718505;178718504;178718503	chr2:179583232;179583231;179583230
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-67
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.3412
• 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
S/P	rs1397176546	-0.071	0.662	N	0.465	0.394	0.337621943819	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	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
S/A	0.0727	likely_benign	0.0714	benign	-0.348	Destabilizing	None	N	0.046	neutral	N	0.489308767	None	None	I
S/C	0.1561	likely_benign	0.1526	benign	-0.401	Destabilizing	0.901	D	0.444	neutral	None	None	None	None	I
S/D	0.2707	likely_benign	0.298	benign	0.053	Stabilizing	0.002	N	0.119	neutral	None	None	None	None	I
S/E	0.3294	likely_benign	0.3598	ambiguous	0.016	Stabilizing	0.007	N	0.113	neutral	None	None	None	None	I
S/F	0.1147	likely_benign	0.1298	benign	-0.656	Destabilizing	0.004	N	0.267	neutral	None	None	None	None	I
S/G	0.1337	likely_benign	0.135	benign	-0.55	Destabilizing	0.103	N	0.23	neutral	None	None	None	None	I
S/H	0.2249	likely_benign	0.2452	benign	-1.01	Destabilizing	0.901	D	0.451	neutral	None	None	None	None	I
S/I	0.1384	likely_benign	0.1475	benign	0.063	Stabilizing	0.39	N	0.469	neutral	None	None	None	None	I
S/K	0.3826	ambiguous	0.4239	ambiguous	-0.627	Destabilizing	0.345	N	0.301	neutral	None	None	None	None	I
S/L	0.0845	likely_benign	0.0876	benign	0.063	Stabilizing	0.064	N	0.273	neutral	N	0.518554239	None	None	I
S/M	0.1651	likely_benign	0.1758	benign	0.094	Stabilizing	0.103	N	0.226	neutral	None	None	None	None	I
S/N	0.1311	likely_benign	0.1402	benign	-0.487	Destabilizing	0.002	N	0.131	neutral	None	None	None	None	I
S/P	0.642	likely_pathogenic	0.6065	pathogenic	-0.041	Destabilizing	0.662	D	0.465	neutral	N	0.517500882	None	None	I
S/Q	0.3344	likely_benign	0.3653	ambiguous	-0.621	Destabilizing	0.561	D	0.313	neutral	None	None	None	None	I
S/R	0.3171	likely_benign	0.3605	ambiguous	-0.486	Destabilizing	0.561	D	0.453	neutral	None	None	None	None	I
S/T	0.0707	likely_benign	0.0737	benign	-0.502	Destabilizing	0.285	N	0.284	neutral	N	0.448576865	None	None	I
S/V	0.1402	likely_benign	0.1461	benign	-0.041	Destabilizing	0.209	N	0.337	neutral	None	None	None	None	I
S/W	0.2564	likely_benign	0.2737	benign	-0.695	Destabilizing	0.991	D	0.507	neutral	None	None	None	None	I
S/Y	0.1159	likely_benign	0.1262	benign	-0.406	Destabilizing	0.39	N	0.573	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.