TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31319	94180;94181;94182	chr2:178547671;178547670;178547669	chr2:179412398;179412397;179412396
N2AB	29678	89257;89258;89259	chr2:178547671;178547670;178547669	chr2:179412398;179412397;179412396
N2A	28751	86476;86477;86478	chr2:178547671;178547670;178547669	chr2:179412398;179412397;179412396
N2B	22254	66985;66986;66987	chr2:178547671;178547670;178547669	chr2:179412398;179412397;179412396
Novex-1	22379	67360;67361;67362	chr2:178547671;178547670;178547669	chr2:179412398;179412397;179412396
Novex-2	22446	67561;67562;67563	chr2:178547671;178547670;178547669	chr2:179412398;179412397;179412396
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: Fn3-116
• Domain position: 12
• Structural Position: 13
• Q(SASA): 0.4321
• 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	0.999	N	0.748	0.455	0.414930877219	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0882	likely_benign	0.0912	benign	-0.428	Destabilizing	0.973	D	0.315	neutral	N	0.514558636	None	None	N
S/C	0.1357	likely_benign	0.1397	benign	-0.351	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
S/D	0.3462	ambiguous	0.3591	ambiguous	0.313	Stabilizing	0.996	D	0.533	neutral	None	None	None	None	N
S/E	0.4484	ambiguous	0.4656	ambiguous	0.224	Stabilizing	0.999	D	0.541	neutral	None	None	None	None	N
S/F	0.1658	likely_benign	0.186	benign	-0.97	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
S/G	0.12	likely_benign	0.1058	benign	-0.547	Destabilizing	0.134	N	0.183	neutral	None	None	None	None	N
S/H	0.3063	likely_benign	0.3082	benign	-1.044	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
S/I	0.1816	likely_benign	0.1935	benign	-0.245	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
S/K	0.5585	ambiguous	0.5972	pathogenic	-0.465	Destabilizing	0.996	D	0.56	neutral	None	None	None	None	N
S/L	0.1009	likely_benign	0.1156	benign	-0.245	Destabilizing	0.999	D	0.66	neutral	N	0.468055555	None	None	N
S/M	0.1873	likely_benign	0.1906	benign	-0.023	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
S/N	0.1562	likely_benign	0.1545	benign	-0.223	Destabilizing	0.996	D	0.534	neutral	None	None	None	None	N
S/P	0.8705	likely_pathogenic	0.8478	pathogenic	-0.277	Destabilizing	0.999	D	0.748	deleterious	N	0.488288633	None	None	N
S/Q	0.4244	ambiguous	0.4315	ambiguous	-0.463	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
S/R	0.5293	ambiguous	0.5699	pathogenic	-0.292	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
S/T	0.0693	likely_benign	0.0698	benign	-0.357	Destabilizing	0.994	D	0.433	neutral	N	0.435633706	None	None	N
S/V	0.1708	likely_benign	0.176	benign	-0.277	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
S/W	0.3998	ambiguous	0.4367	ambiguous	-0.95	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
S/Y	0.1914	likely_benign	0.2112	benign	-0.68	Destabilizing	1.0	D	0.747	deleterious	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.