TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3863	11812;11813;11814	chr2:178741646;178741645;178741644	chr2:179606373;179606372;179606371
N2AB	3546	10861;10862;10863	chr2:178741646;178741645;178741644	chr2:179606373;179606372;179606371
N2A	None	None	chr2:None	chr2:None
N2B	3500	10723;10724;10725	chr2:178741646;178741645;178741644	chr2:179606373;179606372;179606371
Novex-1	3625	11098;11099;11100	chr2:178741646;178741645;178741644	chr2:179606373;179606372;179606371
Novex-2	3692	11299;11300;11301	chr2:178741646;178741645;178741644	chr2:179606373;179606372;179606371
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-27
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.2592
• 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	None	None	0.997	D	0.595	0.414	None	gnomAD-4.0.0	6.84196E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9946E-07	0	0
S/Y	None	None	0.997	D	0.581	0.414	None	gnomAD-4.0.0	6.84196E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15931E-05	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	0.1217	likely_benign	0.1198	benign	-0.309	Destabilizing	0.76	D	0.346	neutral	N	0.442927287	None	None	I
S/C	0.1728	likely_benign	0.1631	benign	-0.278	Destabilizing	0.1	N	0.359	neutral	D	0.606993599	None	None	I
S/D	0.6348	likely_pathogenic	0.5776	pathogenic	0.538	Stabilizing	0.998	D	0.443	neutral	None	None	None	None	I
S/E	0.8231	likely_pathogenic	0.7854	pathogenic	0.47	Stabilizing	0.998	D	0.453	neutral	None	None	None	None	I
S/F	0.4666	ambiguous	0.3821	ambiguous	-0.857	Destabilizing	0.997	D	0.595	neutral	D	0.605738348	None	None	I
S/G	0.1538	likely_benign	0.135	benign	-0.441	Destabilizing	0.976	D	0.379	neutral	None	None	None	None	I
S/H	0.6487	likely_pathogenic	0.6025	pathogenic	-0.832	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	I
S/I	0.5308	ambiguous	0.4623	ambiguous	-0.09	Destabilizing	0.986	D	0.6	neutral	None	None	None	None	I
S/K	0.9116	likely_pathogenic	0.8813	pathogenic	-0.3	Destabilizing	0.998	D	0.424	neutral	None	None	None	None	I
S/L	0.2004	likely_benign	0.166	benign	-0.09	Destabilizing	0.91	D	0.512	neutral	None	None	None	None	I
S/M	0.4082	ambiguous	0.3811	ambiguous	-0.077	Destabilizing	0.999	D	0.476	neutral	None	None	None	None	I
S/N	0.3124	likely_benign	0.2922	benign	-0.104	Destabilizing	0.998	D	0.481	neutral	None	None	None	None	I
S/P	0.8896	likely_pathogenic	0.8101	pathogenic	-0.133	Destabilizing	0.997	D	0.477	neutral	N	0.517809986	None	None	I
S/Q	0.8227	likely_pathogenic	0.7976	pathogenic	-0.249	Destabilizing	0.998	D	0.426	neutral	None	None	None	None	I
S/R	0.8525	likely_pathogenic	0.8003	pathogenic	-0.167	Destabilizing	0.998	D	0.471	neutral	None	None	None	None	I
S/T	0.1287	likely_benign	0.1203	benign	-0.208	Destabilizing	0.939	D	0.405	neutral	N	0.461139953	None	None	I
S/V	0.4512	ambiguous	0.3955	ambiguous	-0.133	Destabilizing	0.986	D	0.544	neutral	None	None	None	None	I
S/W	0.7455	likely_pathogenic	0.6619	pathogenic	-0.903	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
S/Y	0.447	ambiguous	0.3581	ambiguous	-0.59	Destabilizing	0.997	D	0.581	neutral	D	0.565764985	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.