TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7004	21235;21236;21237	chr2:178724365;178724364;178724363	chr2:179589092;179589091;179589090
N2AB	6687	20284;20285;20286	chr2:178724365;178724364;178724363	chr2:179589092;179589091;179589090
N2A	5760	17503;17504;17505	chr2:178724365;178724364;178724363	chr2:179589092;179589091;179589090
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: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-54
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1646
• 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/F	None	None	0.484	D	0.619	0.347	0.631438196984	gnomAD-4.0.0	6.84325E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99591E-07	0	0
S/Y	None	None	0.484	D	0.612	0.36	0.636706105328	gnomAD-4.0.0	6.84325E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65717E-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
S/A	0.0952	likely_benign	0.0914	benign	-0.895	Destabilizing	0.012	N	0.421	neutral	N	0.516167294	None	None	N
S/C	0.1262	likely_benign	0.1251	benign	-0.749	Destabilizing	0.78	D	0.608	neutral	N	0.49404103	None	None	N
S/D	0.6362	likely_pathogenic	0.5962	pathogenic	-1.404	Destabilizing	0.149	N	0.561	neutral	None	None	None	None	N
S/E	0.633	likely_pathogenic	0.6013	pathogenic	-1.243	Destabilizing	0.149	N	0.573	neutral	None	None	None	None	N
S/F	0.2425	likely_benign	0.2109	benign	-0.867	Destabilizing	0.484	N	0.619	neutral	D	0.528712517	None	None	N
S/G	0.1051	likely_benign	0.1099	benign	-1.257	Destabilizing	0.067	N	0.545	neutral	None	None	None	None	N
S/H	0.3782	ambiguous	0.3445	ambiguous	-1.625	Destabilizing	0.791	D	0.602	neutral	None	None	None	None	N
S/I	0.1603	likely_benign	0.1598	benign	0.012	Stabilizing	0.081	N	0.609	neutral	None	None	None	None	N
S/K	0.7294	likely_pathogenic	0.6974	pathogenic	-0.287	Destabilizing	0.002	N	0.32	neutral	None	None	None	None	N
S/L	0.129	likely_benign	0.1243	benign	0.012	Stabilizing	0.035	N	0.559	neutral	None	None	None	None	N
S/M	0.2053	likely_benign	0.1877	benign	0.001	Stabilizing	0.555	D	0.6	neutral	None	None	None	None	N
S/N	0.1946	likely_benign	0.1711	benign	-0.894	Destabilizing	0.149	N	0.581	neutral	None	None	None	None	N
S/P	0.9271	likely_pathogenic	0.9088	pathogenic	-0.256	Destabilizing	0.484	N	0.589	neutral	N	0.514360557	None	None	N
S/Q	0.5383	ambiguous	0.5115	ambiguous	-0.769	Destabilizing	0.38	N	0.593	neutral	None	None	None	None	N
S/R	0.5993	likely_pathogenic	0.576	pathogenic	-0.556	Destabilizing	0.081	N	0.564	neutral	None	None	None	None	N
S/T	0.0803	likely_benign	0.074	benign	-0.616	Destabilizing	None	N	0.288	neutral	N	0.437394293	None	None	N
S/V	0.1812	likely_benign	0.1711	benign	-0.256	Destabilizing	0.001	N	0.477	neutral	None	None	None	None	N
S/W	0.4071	ambiguous	0.3853	ambiguous	-1.047	Destabilizing	0.935	D	0.702	prob.neutral	None	None	None	None	N
S/Y	0.2264	likely_benign	0.207	benign	-0.621	Destabilizing	0.484	N	0.612	neutral	D	0.532830258	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.