TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26993	81202;81203;81204	chr2:178565155;178565154;178565153	chr2:179429882;179429881;179429880
N2AB	25352	76279;76280;76281	chr2:178565155;178565154;178565153	chr2:179429882;179429881;179429880
N2A	24425	73498;73499;73500	chr2:178565155;178565154;178565153	chr2:179429882;179429881;179429880
N2B	17928	54007;54008;54009	chr2:178565155;178565154;178565153	chr2:179429882;179429881;179429880
Novex-1	18053	54382;54383;54384	chr2:178565155;178565154;178565153	chr2:179429882;179429881;179429880
Novex-2	18120	54583;54584;54585	chr2:178565155;178565154;178565153	chr2:179429882;179429881;179429880
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: Fn3-84
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.2154
• 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	1.0	D	0.807	0.54	0.48461828368	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	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	0.175	likely_benign	0.1666	benign	-0.798	Destabilizing	0.997	D	0.482	neutral	N	0.487416487	None	None	N
S/C	0.1927	likely_benign	0.1958	benign	-0.675	Destabilizing	1.0	D	0.824	deleterious	N	0.503763223	None	None	N
S/D	0.8827	likely_pathogenic	0.8735	pathogenic	-1.455	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
S/E	0.8668	likely_pathogenic	0.8553	pathogenic	-1.285	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
S/F	0.5315	ambiguous	0.5182	ambiguous	-0.692	Destabilizing	1.0	D	0.885	deleterious	N	0.518651474	None	None	N
S/G	0.2086	likely_benign	0.1856	benign	-1.17	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
S/H	0.5812	likely_pathogenic	0.5736	pathogenic	-1.584	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
S/I	0.6033	likely_pathogenic	0.5989	pathogenic	0.134	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
S/K	0.8944	likely_pathogenic	0.8858	pathogenic	-0.411	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
S/L	0.3252	likely_benign	0.3272	benign	0.134	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
S/M	0.473	ambiguous	0.4549	ambiguous	0.028	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
S/N	0.4906	ambiguous	0.4632	ambiguous	-1.036	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
S/P	0.9882	likely_pathogenic	0.9855	pathogenic	-0.142	Destabilizing	1.0	D	0.807	deleterious	D	0.541528669	None	None	N
S/Q	0.7449	likely_pathogenic	0.731	pathogenic	-0.837	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
S/R	0.8337	likely_pathogenic	0.8297	pathogenic	-0.718	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
S/T	0.1479	likely_benign	0.1433	benign	-0.703	Destabilizing	0.999	D	0.529	neutral	D	0.524159554	None	None	N
S/V	0.5507	ambiguous	0.5421	ambiguous	-0.142	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
S/W	0.7255	likely_pathogenic	0.7232	pathogenic	-0.96	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
S/Y	0.516	ambiguous	0.5165	ambiguous	-0.51	Destabilizing	1.0	D	0.891	deleterious	N	0.518651474	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.