TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14574	43945;43946;43947	chr2:178632174;178632173;178632172	chr2:179496901;179496900;179496899
N2AB	12933	39022;39023;39024	chr2:178632174;178632173;178632172	chr2:179496901;179496900;179496899
N2A	12006	36241;36242;36243	chr2:178632174;178632173;178632172	chr2:179496901;179496900;179496899
N2B	5509	16750;16751;16752	chr2:178632174;178632173;178632172	chr2:179496901;179496900;179496899
Novex-1	5634	17125;17126;17127	chr2:178632174;178632173;178632172	chr2:179496901;179496900;179496899
Novex-2	5701	17326;17327;17328	chr2:178632174;178632173;178632172	chr2:179496901;179496900;179496899
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-96
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.4291
• 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/N	None	None	0.505	N	0.645	0.147	0.238096912614	gnomAD-4.0.0	1.60748E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88386E-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	0.083	likely_benign	0.0774	benign	-0.686	Destabilizing	0.004	N	0.35	neutral	None	None	None	None	N
S/C	0.1261	likely_benign	0.1339	benign	-0.461	Destabilizing	0.965	D	0.693	prob.neutral	D	0.551611821	None	None	N
S/D	0.4517	ambiguous	0.4112	ambiguous	0.123	Stabilizing	0.575	D	0.627	neutral	None	None	None	None	N
S/E	0.5069	ambiguous	0.4462	ambiguous	0.106	Stabilizing	0.575	D	0.631	neutral	None	None	None	None	N
S/F	0.1705	likely_benign	0.1601	benign	-0.895	Destabilizing	0.906	D	0.783	deleterious	None	None	None	None	N
S/G	0.139	likely_benign	0.1346	benign	-0.917	Destabilizing	0.338	N	0.642	neutral	D	0.547333665	None	None	N
S/H	0.3231	likely_benign	0.3244	benign	-1.299	Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	N
S/I	0.1495	likely_benign	0.1334	benign	-0.186	Destabilizing	0.642	D	0.765	deleterious	N	0.50414849	None	None	N
S/K	0.6309	likely_pathogenic	0.59	pathogenic	-0.603	Destabilizing	0.575	D	0.634	neutral	None	None	None	None	N
S/L	0.1198	likely_benign	0.113	benign	-0.186	Destabilizing	0.404	N	0.742	deleterious	None	None	None	None	N
S/M	0.238	likely_benign	0.2191	benign	-0.02	Destabilizing	0.973	D	0.697	prob.neutral	None	None	None	None	N
S/N	0.1624	likely_benign	0.1563	benign	-0.483	Destabilizing	0.505	D	0.645	neutral	N	0.497452452	None	None	N
S/P	0.5088	ambiguous	0.5076	ambiguous	-0.319	Destabilizing	0.906	D	0.705	prob.neutral	None	None	None	None	N
S/Q	0.5024	ambiguous	0.4725	ambiguous	-0.625	Destabilizing	0.906	D	0.659	neutral	None	None	None	None	N
S/R	0.5021	ambiguous	0.4744	ambiguous	-0.469	Destabilizing	0.782	D	0.717	prob.delet.	N	0.504373671	None	None	N
S/T	0.0791	likely_benign	0.0718	benign	-0.56	Destabilizing	0.001	N	0.313	neutral	N	0.466852122	None	None	N
S/V	0.1618	likely_benign	0.1449	benign	-0.319	Destabilizing	0.404	N	0.752	deleterious	None	None	None	None	N
S/W	0.3288	likely_benign	0.3241	benign	-0.854	Destabilizing	0.991	D	0.749	deleterious	None	None	None	None	N
S/Y	0.1637	likely_benign	0.1572	benign	-0.598	Destabilizing	0.906	D	0.784	deleterious	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.