TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19456	58591;58592;58593	chr2:178594027;178594026;178594025	chr2:179458754;179458753;179458752
N2AB	17815	53668;53669;53670	chr2:178594027;178594026;178594025	chr2:179458754;179458753;179458752
N2A	16888	50887;50888;50889	chr2:178594027;178594026;178594025	chr2:179458754;179458753;179458752
N2B	10391	31396;31397;31398	chr2:178594027;178594026;178594025	chr2:179458754;179458753;179458752
Novex-1	10516	31771;31772;31773	chr2:178594027;178594026;178594025	chr2:179458754;179458753;179458752
Novex-2	10583	31972;31973;31974	chr2:178594027;178594026;178594025	chr2:179458754;179458753;179458752
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-118
• Domain position: 66
• Structural Position: 153
• Q(SASA): 0.5793
• 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
K/R	None	None	0.002	N	0.173	0.091	0.232513804876	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.3855	ambiguous	0.3745	ambiguous	-0.745	Destabilizing	0.4	N	0.433	neutral	None	None	None	None	N
K/C	0.6357	likely_pathogenic	0.6486	pathogenic	-0.643	Destabilizing	0.005	N	0.379	neutral	None	None	None	None	N
K/D	0.5307	ambiguous	0.4935	ambiguous	-0.278	Destabilizing	0.85	D	0.557	neutral	None	None	None	None	N
K/E	0.2068	likely_benign	0.1859	benign	-0.141	Destabilizing	0.379	N	0.424	neutral	N	0.501755202	None	None	N
K/F	0.6746	likely_pathogenic	0.6677	pathogenic	-0.334	Destabilizing	0.85	D	0.571	neutral	None	None	None	None	N
K/G	0.5714	likely_pathogenic	0.5569	ambiguous	-1.142	Destabilizing	0.617	D	0.521	neutral	None	None	None	None	N
K/H	0.282	likely_benign	0.2847	benign	-1.515	Destabilizing	0.92	D	0.549	neutral	None	None	None	None	N
K/I	0.2221	likely_benign	0.2179	benign	0.301	Stabilizing	0.379	N	0.557	neutral	D	0.524786778	None	None	N
K/L	0.2688	likely_benign	0.271	benign	0.301	Stabilizing	0.005	N	0.311	neutral	None	None	None	None	N
K/M	0.1806	likely_benign	0.1799	benign	0.222	Stabilizing	0.85	D	0.553	neutral	None	None	None	None	N
K/N	0.3186	likely_benign	0.2947	benign	-0.653	Destabilizing	0.549	D	0.476	neutral	D	0.524786778	None	None	N
K/P	0.7309	likely_pathogenic	0.7337	pathogenic	-0.018	Destabilizing	0.92	D	0.566	neutral	None	None	None	None	N
K/Q	0.1486	likely_benign	0.1475	benign	-0.665	Destabilizing	0.81	D	0.501	neutral	N	0.4967921	None	None	N
K/R	0.0797	likely_benign	0.081	benign	-0.787	Destabilizing	0.002	N	0.173	neutral	N	0.481246644	None	None	N
K/S	0.4034	ambiguous	0.3783	ambiguous	-1.307	Destabilizing	0.617	D	0.417	neutral	None	None	None	None	N
K/T	0.1375	likely_benign	0.1323	benign	-0.951	Destabilizing	0.549	D	0.493	neutral	N	0.495618664	None	None	N
K/V	0.2342	likely_benign	0.2395	benign	-0.018	Destabilizing	0.447	N	0.523	neutral	None	None	None	None	N
K/W	0.6832	likely_pathogenic	0.6561	pathogenic	-0.216	Destabilizing	0.992	D	0.558	neutral	None	None	None	None	N
K/Y	0.5136	ambiguous	0.5113	ambiguous	0.063	Stabilizing	0.972	D	0.57	neutral	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.