TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7767	23524;23525;23526	chr2:178720463;178720462;178720461	chr2:179585190;179585189;179585188
N2AB	7450	22573;22574;22575	chr2:178720463;178720462;178720461	chr2:179585190;179585189;179585188
N2A	6523	19792;19793;19794	chr2:178720463;178720462;178720461	chr2:179585190;179585189;179585188
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: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-62
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.3739
• 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/F	None	None	0.171	N	0.405	0.209	0.406668915854	gnomAD-4.0.0	1.59163E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85909E-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	0.0542	likely_benign	0.055	benign	-0.176	Destabilizing	None	N	0.093	neutral	N	0.435681273	None	None	N
S/C	0.1721	likely_benign	0.1808	benign	-0.317	Destabilizing	0.295	N	0.348	neutral	N	0.507806514	None	None	N
S/D	0.394	ambiguous	0.537	ambiguous	0.174	Stabilizing	0.038	N	0.203	neutral	None	None	None	None	N
S/E	0.4823	ambiguous	0.6197	pathogenic	0.084	Stabilizing	0.016	N	0.213	neutral	None	None	None	None	N
S/F	0.1837	likely_benign	0.2161	benign	-0.829	Destabilizing	0.171	N	0.405	neutral	N	0.475459118	None	None	N
S/G	0.0755	likely_benign	0.0897	benign	-0.27	Destabilizing	0.016	N	0.24	neutral	None	None	None	None	N
S/H	0.3159	likely_benign	0.4221	ambiguous	-0.633	Destabilizing	0.356	N	0.363	neutral	None	None	None	None	N
S/I	0.1326	likely_benign	0.1568	benign	-0.064	Destabilizing	0.038	N	0.412	neutral	None	None	None	None	N
S/K	0.6	likely_pathogenic	0.7519	pathogenic	-0.374	Destabilizing	0.016	N	0.206	neutral	None	None	None	None	N
S/L	0.0776	likely_benign	0.0861	benign	-0.064	Destabilizing	None	N	0.247	neutral	None	None	None	None	N
S/M	0.1379	likely_benign	0.1624	benign	-0.047	Destabilizing	0.214	N	0.363	neutral	None	None	None	None	N
S/N	0.1102	likely_benign	0.146	benign	-0.173	Destabilizing	0.001	N	0.191	neutral	None	None	None	None	N
S/P	0.1019	likely_benign	0.1244	benign	-0.073	Destabilizing	None	N	0.212	neutral	N	0.469445184	None	None	N
S/Q	0.3533	ambiguous	0.4664	ambiguous	-0.367	Destabilizing	0.001	N	0.195	neutral	None	None	None	None	N
S/R	0.5912	likely_pathogenic	0.7334	pathogenic	-0.14	Destabilizing	0.038	N	0.423	neutral	None	None	None	None	N
S/T	0.073	likely_benign	0.0775	benign	-0.254	Destabilizing	0.001	N	0.145	neutral	N	0.484512583	None	None	N
S/V	0.1223	likely_benign	0.1382	benign	-0.073	Destabilizing	0.016	N	0.331	neutral	None	None	None	None	N
S/W	0.3756	ambiguous	0.4185	ambiguous	-0.905	Destabilizing	0.864	D	0.402	neutral	None	None	None	None	N
S/Y	0.2458	likely_benign	0.2742	benign	-0.585	Destabilizing	0.295	N	0.399	neutral	N	0.481054979	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.