TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8802	26629;26630;26631	chr2:178714370;178714369;178714368	chr2:179579097;179579096;179579095
N2AB	8485	25678;25679;25680	chr2:178714370;178714369;178714368	chr2:179579097;179579096;179579095
N2A	7558	22897;22898;22899	chr2:178714370;178714369;178714368	chr2:179579097;179579096;179579095
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-73
• Domain position: 67
• Structural Position: 148
• Q(SASA): 0.3668
• 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
A/D	rs1292226345	-0.737	0.013	N	0.337	0.096	0.258283824007	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
A/D	rs1292226345	-0.737	0.013	N	0.337	0.096	0.258283824007	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85853E-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
A/C	0.4523	ambiguous	0.4221	ambiguous	-0.682	Destabilizing	0.743	D	0.317	neutral	None	None	None	None	N
A/D	0.1501	likely_benign	0.1454	benign	-0.661	Destabilizing	0.013	N	0.337	neutral	N	0.46380645	None	None	N
A/E	0.142	likely_benign	0.1284	benign	-0.817	Destabilizing	None	N	0.175	neutral	None	None	None	None	N
A/F	0.2213	likely_benign	0.2348	benign	-0.882	Destabilizing	0.484	N	0.354	neutral	None	None	None	None	N
A/G	0.0979	likely_benign	0.0967	benign	-0.244	Destabilizing	None	N	0.155	neutral	N	0.501652762	None	None	N
A/H	0.3174	likely_benign	0.3047	benign	-0.292	Destabilizing	0.78	D	0.327	neutral	None	None	None	None	N
A/I	0.1372	likely_benign	0.1576	benign	-0.301	Destabilizing	0.188	N	0.321	neutral	None	None	None	None	N
A/K	0.2255	likely_benign	0.2227	benign	-0.649	Destabilizing	0.062	N	0.29	neutral	None	None	None	None	N
A/L	0.1147	likely_benign	0.1208	benign	-0.301	Destabilizing	0.062	N	0.309	neutral	None	None	None	None	N
A/M	0.1513	likely_benign	0.1675	benign	-0.384	Destabilizing	0.78	D	0.292	neutral	None	None	None	None	N
A/N	0.1432	likely_benign	0.1477	benign	-0.279	Destabilizing	0.004	N	0.372	neutral	None	None	None	None	N
A/P	0.1586	likely_benign	0.1685	benign	-0.238	Destabilizing	0.159	N	0.307	neutral	N	0.473556106	None	None	N
A/Q	0.2036	likely_benign	0.1948	benign	-0.574	Destabilizing	0.188	N	0.323	neutral	None	None	None	None	N
A/R	0.2265	likely_benign	0.2136	benign	-0.154	Destabilizing	0.317	N	0.321	neutral	None	None	None	None	N
A/S	0.0813	likely_benign	0.0783	benign	-0.43	Destabilizing	None	N	0.125	neutral	N	0.424439985	None	None	N
A/T	0.0718	likely_benign	0.0787	benign	-0.514	Destabilizing	None	N	0.1	neutral	N	0.440777662	None	None	N
A/V	0.0918	likely_benign	0.098	benign	-0.238	Destabilizing	0.018	N	0.255	neutral	N	0.473809596	None	None	N
A/W	0.5396	ambiguous	0.5246	ambiguous	-1.03	Destabilizing	0.915	D	0.424	neutral	None	None	None	None	N
A/Y	0.3361	likely_benign	0.3322	benign	-0.681	Destabilizing	0.741	D	0.345	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.