TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7445	22558;22559;22560	chr2:178722454;178722453;178722452	chr2:179587181;179587180;179587179
N2AB	7128	21607;21608;21609	chr2:178722454;178722453;178722452	chr2:179587181;179587180;179587179
N2A	6201	18826;18827;18828	chr2:178722454;178722453;178722452	chr2:179587181;179587180;179587179
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-59
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5794
• 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/T	None	None	0.2	N	0.276	0.175	0.186928172975	gnomAD-4.0.0	1.59199E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4332E-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	0.1938	likely_benign	0.176	benign	-0.08	Destabilizing	0.136	N	0.239	neutral	N	0.495403247	None	None	I
S/C	0.5073	ambiguous	0.4604	ambiguous	-0.369	Destabilizing	1.0	D	0.541	neutral	N	0.512661809	None	None	I
S/D	0.7444	likely_pathogenic	0.7357	pathogenic	0.066	Stabilizing	0.998	D	0.488	neutral	None	None	None	None	I
S/E	0.8956	likely_pathogenic	0.8669	pathogenic	-0.024	Destabilizing	0.998	D	0.498	neutral	None	None	None	None	I
S/F	0.5473	ambiguous	0.5086	ambiguous	-0.784	Destabilizing	1.0	D	0.685	prob.neutral	N	0.494468649	None	None	I
S/G	0.2212	likely_benign	0.221	benign	-0.15	Destabilizing	0.997	D	0.453	neutral	None	None	None	None	I
S/H	0.7799	likely_pathogenic	0.7561	pathogenic	-0.417	Destabilizing	1.0	D	0.539	neutral	None	None	None	None	I
S/I	0.6325	likely_pathogenic	0.5297	ambiguous	-0.029	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
S/K	0.9563	likely_pathogenic	0.9433	pathogenic	-0.335	Destabilizing	0.999	D	0.494	neutral	None	None	None	None	I
S/L	0.3093	likely_benign	0.2639	benign	-0.029	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
S/M	0.5518	ambiguous	0.4954	ambiguous	-0.183	Destabilizing	1.0	D	0.53	neutral	None	None	None	None	I
S/N	0.4346	ambiguous	0.4248	ambiguous	-0.09	Destabilizing	0.98	D	0.519	neutral	None	None	None	None	I
S/P	0.8412	likely_pathogenic	0.7934	pathogenic	-0.02	Destabilizing	0.999	D	0.534	neutral	N	0.517434749	None	None	I
S/Q	0.8849	likely_pathogenic	0.8587	pathogenic	-0.282	Destabilizing	1.0	D	0.475	neutral	None	None	None	None	I
S/R	0.9227	likely_pathogenic	0.9093	pathogenic	-0.074	Destabilizing	1.0	D	0.532	neutral	None	None	None	None	I
S/T	0.1537	likely_benign	0.1412	benign	-0.173	Destabilizing	0.2	N	0.276	neutral	N	0.517858018	None	None	I
S/V	0.595	likely_pathogenic	0.5004	ambiguous	-0.02	Destabilizing	0.997	D	0.629	neutral	None	None	None	None	I
S/W	0.7454	likely_pathogenic	0.7112	pathogenic	-0.899	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
S/Y	0.5672	likely_pathogenic	0.5163	ambiguous	-0.557	Destabilizing	1.0	D	0.677	prob.neutral	N	0.490683214	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.