TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5492	16699;16700;16701	chr2:178732587;178732586;178732585	chr2:179597314;179597313;179597312
N2AB	5175	15748;15749;15750	chr2:178732587;178732586;178732585	chr2:179597314;179597313;179597312
N2A	4248	12967;12968;12969	chr2:178732587;178732586;178732585	chr2:179597314;179597313;179597312
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-38
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.8799
• 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/F	rs1162269961	None	0.984	N	0.569	0.495	0.752771577926	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.92976E-04	None	0	0	0	0	0
S/F	rs1162269961	None	0.984	N	0.569	0.495	0.752771577926	gnomAD-4.0.0	2.56274E-06	None	None	None	None	I	None	0	0	None	0	2.4273E-05	None	0	0	0	1.34005E-05	0
S/P	None	None	0.984	N	0.428	0.345	0.346544149963	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	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	0.0818	likely_benign	0.0924	benign	-0.336	Destabilizing	0.64	D	0.341	neutral	N	0.51641801	None	None	I
S/C	0.1666	likely_benign	0.2021	benign	-0.368	Destabilizing	0.999	D	0.475	neutral	N	0.521072508	None	None	I
S/D	0.4466	ambiguous	0.6083	pathogenic	0.512	Stabilizing	0.919	D	0.305	neutral	None	None	None	None	I
S/E	0.5103	ambiguous	0.667	pathogenic	0.431	Stabilizing	0.919	D	0.317	neutral	None	None	None	None	I
S/F	0.255	likely_benign	0.3901	ambiguous	-0.916	Destabilizing	0.984	D	0.569	neutral	N	0.498359897	None	None	I
S/G	0.1104	likely_benign	0.1295	benign	-0.445	Destabilizing	0.919	D	0.327	neutral	None	None	None	None	I
S/H	0.4256	ambiguous	0.5526	ambiguous	-0.768	Destabilizing	0.999	D	0.457	neutral	None	None	None	None	I
S/I	0.2225	likely_benign	0.3334	benign	-0.182	Destabilizing	0.976	D	0.556	neutral	None	None	None	None	I
S/K	0.6582	likely_pathogenic	0.8175	pathogenic	-0.321	Destabilizing	0.919	D	0.307	neutral	None	None	None	None	I
S/L	0.1039	likely_benign	0.1401	benign	-0.182	Destabilizing	0.851	D	0.443	neutral	None	None	None	None	I
S/M	0.2257	likely_benign	0.2823	benign	-0.188	Destabilizing	0.999	D	0.448	neutral	None	None	None	None	I
S/N	0.1929	likely_benign	0.2535	benign	-0.117	Destabilizing	0.919	D	0.355	neutral	None	None	None	None	I
S/P	0.0804	likely_benign	0.0845	benign	-0.205	Destabilizing	0.984	D	0.428	neutral	N	0.459583293	None	None	I
S/Q	0.526	ambiguous	0.6337	pathogenic	-0.29	Destabilizing	0.988	D	0.355	neutral	None	None	None	None	I
S/R	0.5722	likely_pathogenic	0.7551	pathogenic	-0.132	Destabilizing	0.976	D	0.432	neutral	None	None	None	None	I
S/T	0.078	likely_benign	0.0982	benign	-0.248	Destabilizing	0.046	N	0.171	neutral	N	0.510396115	None	None	I
S/V	0.2239	likely_benign	0.3125	benign	-0.205	Destabilizing	0.851	D	0.441	neutral	None	None	None	None	I
S/W	0.3257	likely_benign	0.4596	ambiguous	-0.946	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
S/Y	0.2152	likely_benign	0.33	benign	-0.643	Destabilizing	0.995	D	0.563	neutral	N	0.487737607	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.