TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26276	79051;79052;79053	chr2:178567306;178567305;178567304	chr2:179432033;179432032;179432031
N2AB	24635	74128;74129;74130	chr2:178567306;178567305;178567304	chr2:179432033;179432032;179432031
N2A	23708	71347;71348;71349	chr2:178567306;178567305;178567304	chr2:179432033;179432032;179432031
N2B	17211	51856;51857;51858	chr2:178567306;178567305;178567304	chr2:179432033;179432032;179432031
Novex-1	17336	52231;52232;52233	chr2:178567306;178567305;178567304	chr2:179432033;179432032;179432031
Novex-2	17403	52432;52433;52434	chr2:178567306;178567305;178567304	chr2:179432033;179432032;179432031
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-137
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.3826
• 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
S/P	None	None	0.939	D	0.511	0.556	0.346544149963	gnomAD-4.0.0	6.87401E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0139E-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
S/A	0.0951	likely_benign	0.0872	benign	-0.438	Destabilizing	0.003	N	0.145	neutral	N	0.488872788	None	None	N
S/C	0.1158	likely_benign	0.103	benign	-0.383	Destabilizing	0.987	D	0.493	neutral	None	None	None	None	N
S/D	0.4416	ambiguous	0.3855	ambiguous	0.278	Stabilizing	0.742	D	0.431	neutral	None	None	None	None	N
S/E	0.452	ambiguous	0.412	ambiguous	0.303	Stabilizing	0.742	D	0.417	neutral	None	None	None	None	N
S/F	0.2115	likely_benign	0.1746	benign	-0.65	Destabilizing	0.953	D	0.589	neutral	None	None	None	None	N
S/G	0.151	likely_benign	0.1358	benign	-0.696	Destabilizing	0.373	N	0.475	neutral	None	None	None	None	N
S/H	0.3225	likely_benign	0.2835	benign	-1.087	Destabilizing	0.996	D	0.493	neutral	None	None	None	None	N
S/I	0.1366	likely_benign	0.1166	benign	0.135	Stabilizing	0.91	D	0.573	neutral	None	None	None	None	N
S/K	0.6514	likely_pathogenic	0.5833	pathogenic	-0.354	Destabilizing	0.742	D	0.41	neutral	None	None	None	None	N
S/L	0.109	likely_benign	0.0962	benign	0.135	Stabilizing	0.521	D	0.547	neutral	N	0.516713961	None	None	N
S/M	0.1555	likely_benign	0.1389	benign	0.051	Stabilizing	0.984	D	0.505	neutral	None	None	None	None	N
S/N	0.1346	likely_benign	0.1204	benign	-0.425	Destabilizing	0.742	D	0.463	neutral	None	None	None	None	N
S/P	0.7369	likely_pathogenic	0.6865	pathogenic	-0.021	Destabilizing	0.939	D	0.511	neutral	D	0.522563311	None	None	N
S/Q	0.4257	ambiguous	0.3835	ambiguous	-0.426	Destabilizing	0.953	D	0.459	neutral	None	None	None	None	N
S/R	0.5914	likely_pathogenic	0.521	ambiguous	-0.384	Destabilizing	0.953	D	0.527	neutral	None	None	None	None	N
S/T	0.0677	likely_benign	0.0629	benign	-0.41	Destabilizing	0.004	N	0.127	neutral	N	0.488284473	None	None	N
S/V	0.14	likely_benign	0.1204	benign	-0.021	Destabilizing	0.59	D	0.544	neutral	None	None	None	None	N
S/W	0.3985	ambiguous	0.3316	benign	-0.72	Destabilizing	0.996	D	0.644	neutral	None	None	None	None	N
S/Y	0.1838	likely_benign	0.1557	benign	-0.378	Destabilizing	0.984	D	0.581	neutral	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.