TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9451	28576;28577;28578	chr2:178710746;178710745;178710744	chr2:179575473;179575472;179575471
N2AB	9134	27625;27626;27627	chr2:178710746;178710745;178710744	chr2:179575473;179575472;179575471
N2A	8207	24844;24845;24846	chr2:178710746;178710745;178710744	chr2:179575473;179575472;179575471
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-80
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2599
• 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/R	rs777096848	-0.591	0.351	None	0.545	0.193	0.0920862733494	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
S/R	rs777096848	-0.591	0.351	None	0.545	0.193	0.0920862733494	gnomAD-4.0.0	6.84188E-07	None	None	None	None	N	None	0	0	None	0	2.51902E-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
S/A	0.0875	likely_benign	0.0936	benign	-0.342	Destabilizing	0.002	N	0.121	neutral	None	None	None	None	N
S/C	0.1435	likely_benign	0.1872	benign	-0.221	Destabilizing	0.001	N	0.303	neutral	None	None	None	None	N
S/D	0.3077	likely_benign	0.4496	ambiguous	-1.508	Destabilizing	0.22	N	0.332	neutral	None	None	None	None	N
S/E	0.3341	likely_benign	0.5391	ambiguous	-1.398	Destabilizing	0.22	N	0.333	neutral	None	None	None	None	N
S/F	0.1625	likely_benign	0.2047	benign	-0.242	Destabilizing	0.497	N	0.603	neutral	None	None	None	None	N
S/G	0.1319	likely_benign	0.1545	benign	-0.683	Destabilizing	0.081	N	0.292	neutral	None	None	None	None	N
S/H	0.1836	likely_benign	0.3367	benign	-1.384	Destabilizing	0.859	D	0.523	neutral	None	None	None	None	N
S/I	0.0799	likely_benign	0.121	benign	0.487	Stabilizing	None	N	0.277	neutral	None	None	None	None	N
S/K	0.2806	likely_benign	0.5681	pathogenic	-0.608	Destabilizing	0.22	N	0.333	neutral	None	None	None	None	N
S/L	0.0912	likely_benign	0.106	benign	0.487	Stabilizing	0.025	N	0.367	neutral	None	None	None	None	N
S/M	0.1435	likely_benign	0.1815	benign	0.653	Stabilizing	0.497	N	0.529	neutral	None	None	None	None	N
S/N	0.1096	likely_benign	0.1605	benign	-1.08	Destabilizing	0.175	N	0.373	neutral	None	None	None	None	N
S/P	0.7519	likely_pathogenic	0.8545	pathogenic	0.246	Stabilizing	0.364	N	0.539	neutral	None	None	None	None	N
S/Q	0.3066	likely_benign	0.519	ambiguous	-0.926	Destabilizing	0.667	D	0.455	neutral	None	None	None	None	N
S/R	0.21	likely_benign	0.434	ambiguous	-0.897	Destabilizing	0.351	N	0.545	neutral	None	None	None	None	N
S/T	0.0544	likely_benign	0.0591	benign	-0.681	Destabilizing	None	N	0.123	neutral	None	None	None	None	N
S/V	0.1133	likely_benign	0.1468	benign	0.246	Stabilizing	0.025	N	0.367	neutral	None	None	None	None	N
S/W	0.249	likely_benign	0.3549	ambiguous	-0.623	Destabilizing	0.958	D	0.588	neutral	None	None	None	None	N
S/Y	0.1342	likely_benign	0.1853	benign	-0.198	Destabilizing	0.667	D	0.599	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.