TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22174	66745;66746;66747	chr2:178581748;178581747;178581746	chr2:179446475;179446474;179446473
N2AB	20533	61822;61823;61824	chr2:178581748;178581747;178581746	chr2:179446475;179446474;179446473
N2A	19606	59041;59042;59043	chr2:178581748;178581747;178581746	chr2:179446475;179446474;179446473
N2B	13109	39550;39551;39552	chr2:178581748;178581747;178581746	chr2:179446475;179446474;179446473
Novex-1	13234	39925;39926;39927	chr2:178581748;178581747;178581746	chr2:179446475;179446474;179446473
Novex-2	13301	40126;40127;40128	chr2:178581748;178581747;178581746	chr2:179446475;179446474;179446473
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-49
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1672
• 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/N	None	None	0.892	N	0.531	0.171	0.218112801441	gnomAD-4.0.0	6.87091E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01962E-07	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	0.1324	likely_benign	0.1257	benign	-0.939	Destabilizing	0.693	D	0.438	neutral	None	None	None	None	N
S/C	0.1263	likely_benign	0.1188	benign	-0.853	Destabilizing	0.999	D	0.738	prob.delet.	N	0.502705904	None	None	N
S/D	0.7788	likely_pathogenic	0.7872	pathogenic	-1.176	Destabilizing	0.916	D	0.522	neutral	None	None	None	None	N
S/E	0.7995	likely_pathogenic	0.8193	pathogenic	-1.09	Destabilizing	0.916	D	0.531	neutral	None	None	None	None	N
S/F	0.2377	likely_benign	0.2314	benign	-0.915	Destabilizing	0.987	D	0.78	deleterious	None	None	None	None	N
S/G	0.2445	likely_benign	0.2438	benign	-1.236	Destabilizing	0.892	D	0.502	neutral	N	0.479575219	None	None	N
S/H	0.4358	ambiguous	0.4445	ambiguous	-1.557	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
S/I	0.2369	likely_benign	0.2293	benign	-0.227	Destabilizing	0.967	D	0.723	prob.delet.	N	0.511747617	None	None	N
S/K	0.8474	likely_pathogenic	0.8667	pathogenic	-0.634	Destabilizing	0.916	D	0.525	neutral	None	None	None	None	N
S/L	0.1412	likely_benign	0.1425	benign	-0.227	Destabilizing	0.845	D	0.621	neutral	None	None	None	None	N
S/M	0.2078	likely_benign	0.2102	benign	-0.177	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
S/N	0.3156	likely_benign	0.3099	benign	-0.92	Destabilizing	0.892	D	0.531	neutral	N	0.497471598	None	None	N
S/P	0.9647	likely_pathogenic	0.9674	pathogenic	-0.432	Destabilizing	0.987	D	0.707	prob.neutral	None	None	None	None	N
S/Q	0.6483	likely_pathogenic	0.6804	pathogenic	-0.989	Destabilizing	0.987	D	0.647	neutral	None	None	None	None	N
S/R	0.7952	likely_pathogenic	0.8128	pathogenic	-0.633	Destabilizing	0.967	D	0.717	prob.delet.	N	0.507725877	None	None	N
S/T	0.0966	likely_benign	0.0911	benign	-0.789	Destabilizing	0.025	N	0.423	neutral	N	0.424203204	None	None	N
S/V	0.2473	likely_benign	0.2441	benign	-0.432	Destabilizing	0.95	D	0.681	prob.neutral	None	None	None	None	N
S/W	0.4446	ambiguous	0.4335	ambiguous	-0.974	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
S/Y	0.2386	likely_benign	0.2368	benign	-0.638	Destabilizing	0.996	D	0.773	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.