TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27861	83806;83807;83808	chr2:178562551;178562550;178562549	chr2:179427278;179427277;179427276
N2AB	26220	78883;78884;78885	chr2:178562551;178562550;178562549	chr2:179427278;179427277;179427276
N2A	25293	76102;76103;76104	chr2:178562551;178562550;178562549	chr2:179427278;179427277;179427276
N2B	18796	56611;56612;56613	chr2:178562551;178562550;178562549	chr2:179427278;179427277;179427276
Novex-1	18921	56986;56987;56988	chr2:178562551;178562550;178562549	chr2:179427278;179427277;179427276
Novex-2	18988	57187;57188;57189	chr2:178562551;178562550;178562549	chr2:179427278;179427277;179427276
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: Fn3-90
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.3225
• 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	1.0	N	0.715	0.333	0.498641525541	gnomAD-4.0.0	3.19901E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.73506E-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	0.0715	likely_benign	0.0773	benign	-0.492	Destabilizing	0.003	N	0.204	neutral	N	0.449346791	None	None	N
S/C	0.112	likely_benign	0.1306	benign	-0.483	Destabilizing	1.0	D	0.515	neutral	N	0.509549887	None	None	N
S/D	0.9445	likely_pathogenic	0.9595	pathogenic	-0.193	Destabilizing	0.992	D	0.541	neutral	None	None	None	None	N
S/E	0.9327	likely_pathogenic	0.9515	pathogenic	-0.252	Destabilizing	0.96	D	0.551	neutral	None	None	None	None	N
S/F	0.5795	likely_pathogenic	0.6277	pathogenic	-0.788	Destabilizing	1.0	D	0.715	prob.delet.	N	0.518438729	None	None	N
S/G	0.1973	likely_benign	0.2334	benign	-0.675	Destabilizing	0.868	D	0.43	neutral	None	None	None	None	N
S/H	0.8691	likely_pathogenic	0.8919	pathogenic	-1.156	Destabilizing	1.0	D	0.509	neutral	None	None	None	None	N
S/I	0.5345	ambiguous	0.6252	pathogenic	-0.13	Destabilizing	1.0	D	0.721	deleterious	None	None	None	None	N
S/K	0.9794	likely_pathogenic	0.9862	pathogenic	-0.788	Destabilizing	0.999	D	0.555	neutral	None	None	None	None	N
S/L	0.2147	likely_benign	0.281	benign	-0.13	Destabilizing	0.997	D	0.562	neutral	None	None	None	None	N
S/M	0.3521	ambiguous	0.4215	ambiguous	0.091	Stabilizing	1.0	D	0.501	neutral	None	None	None	None	N
S/N	0.6603	likely_pathogenic	0.7273	pathogenic	-0.577	Destabilizing	0.935	D	0.576	neutral	None	None	None	None	N
S/P	0.9617	likely_pathogenic	0.9755	pathogenic	-0.219	Destabilizing	0.989	D	0.548	neutral	N	0.487574318	None	None	N
S/Q	0.8822	likely_pathogenic	0.9045	pathogenic	-0.824	Destabilizing	0.998	D	0.524	neutral	None	None	None	None	N
S/R	0.9554	likely_pathogenic	0.9693	pathogenic	-0.553	Destabilizing	1.0	D	0.544	neutral	None	None	None	None	N
S/T	0.1544	likely_benign	0.1802	benign	-0.644	Destabilizing	0.198	N	0.464	neutral	N	0.518092013	None	None	N
S/V	0.3892	ambiguous	0.4633	ambiguous	-0.219	Destabilizing	0.992	D	0.535	neutral	None	None	None	None	N
S/W	0.7889	likely_pathogenic	0.815	pathogenic	-0.755	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
S/Y	0.6151	likely_pathogenic	0.669	pathogenic	-0.516	Destabilizing	1.0	D	0.697	prob.delet.	N	0.485822054	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.