TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5125	15598;15599;15600	chr2:178734451;178734450;178734449	chr2:179599178;179599177;179599176
N2AB	4808	14647;14648;14649	chr2:178734451;178734450;178734449	chr2:179599178;179599177;179599176
N2A	3881	11866;11867;11868	chr2:178734451;178734450;178734449	chr2:179599178;179599177;179599176
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-34
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.42
• 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/C	None	None	0.484	D	0.635	0.337	0.478755181577	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85869E-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	0.0684	likely_benign	0.0749	benign	-0.464	Destabilizing	None	N	0.262	neutral	N	0.505093142	None	None	N
S/C	0.0918	likely_benign	0.0964	benign	-0.325	Destabilizing	0.484	N	0.635	neutral	D	0.639462161	None	None	N
S/D	0.4056	ambiguous	0.4685	ambiguous	0.526	Stabilizing	0.149	N	0.598	neutral	None	None	None	None	N
S/E	0.4681	ambiguous	0.5273	ambiguous	0.458	Stabilizing	0.149	N	0.553	neutral	None	None	None	None	N
S/F	0.1133	likely_benign	0.1488	benign	-0.991	Destabilizing	0.317	N	0.721	prob.delet.	N	0.512031569	None	None	N
S/G	0.1046	likely_benign	0.1223	benign	-0.601	Destabilizing	0.035	N	0.543	neutral	None	None	None	None	N
S/H	0.2531	likely_benign	0.2821	benign	-1.026	Destabilizing	0.935	D	0.63	neutral	None	None	None	None	N
S/I	0.1265	likely_benign	0.1597	benign	-0.23	Destabilizing	0.081	N	0.69	prob.neutral	None	None	None	None	N
S/K	0.5726	likely_pathogenic	0.6503	pathogenic	-0.364	Destabilizing	0.149	N	0.555	neutral	None	None	None	None	N
S/L	0.0755	likely_benign	0.0867	benign	-0.23	Destabilizing	0.001	N	0.458	neutral	None	None	None	None	N
S/M	0.1562	likely_benign	0.1871	benign	-0.146	Destabilizing	0.38	N	0.65	neutral	None	None	None	None	N
S/N	0.1444	likely_benign	0.1719	benign	-0.145	Destabilizing	0.149	N	0.612	neutral	None	None	None	None	N
S/P	0.1915	likely_benign	0.2514	benign	-0.278	Destabilizing	0.484	N	0.656	neutral	N	0.511441714	None	None	N
S/Q	0.3786	ambiguous	0.4259	ambiguous	-0.303	Destabilizing	0.555	D	0.635	neutral	None	None	None	None	N
S/R	0.5071	ambiguous	0.5539	ambiguous	-0.242	Destabilizing	0.38	N	0.661	neutral	None	None	None	None	N
S/T	0.0719	likely_benign	0.0817	benign	-0.26	Destabilizing	None	N	0.257	neutral	N	0.498766577	None	None	N
S/V	0.1226	likely_benign	0.1479	benign	-0.278	Destabilizing	0.002	N	0.461	neutral	None	None	None	None	N
S/W	0.2156	likely_benign	0.2628	benign	-1.001	Destabilizing	0.935	D	0.705	prob.neutral	None	None	None	None	N
S/Y	0.1109	likely_benign	0.138	benign	-0.71	Destabilizing	0.484	N	0.714	prob.delet.	N	0.508845769	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.