TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29734	89425;89426;89427	chr2:178553805;178553804;178553803	chr2:179418532;179418531;179418530
N2AB	28093	84502;84503;84504	chr2:178553805;178553804;178553803	chr2:179418532;179418531;179418530
N2A	27166	81721;81722;81723	chr2:178553805;178553804;178553803	chr2:179418532;179418531;179418530
N2B	20669	62230;62231;62232	chr2:178553805;178553804;178553803	chr2:179418532;179418531;179418530
Novex-1	20794	62605;62606;62607	chr2:178553805;178553804;178553803	chr2:179418532;179418531;179418530
Novex-2	20861	62806;62807;62808	chr2:178553805;178553804;178553803	chr2:179418532;179418531;179418530
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-105
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4953
• Predicted PPI site: I

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
P/L	rs759858087	-0.058	0.001	N	0.171	0.122	0.400033932507	gnomAD-2.1.1	4.43E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.65E-06	0
P/L	rs759858087	-0.058	0.001	N	0.171	0.122	0.400033932507	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	1.31027E-04	0	0	0	None	0	0	0	0	0
P/L	rs759858087	-0.058	0.001	N	0.171	0.122	0.400033932507	gnomAD-4.0.0	1.07093E-05	None	None	None	None	I	None	0	3.48432E-05	None	0	0	None	0	0	1.28597E-05	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
P/A	0.1068	likely_benign	0.1098	benign	-0.568	Destabilizing	0.104	N	0.371	neutral	N	0.482902004	None	None	I
P/C	0.4647	ambiguous	0.4659	ambiguous	-0.602	Destabilizing	0.984	D	0.317	neutral	None	None	None	None	I
P/D	0.7744	likely_pathogenic	0.7842	pathogenic	-0.273	Destabilizing	0.272	N	0.465	neutral	None	None	None	None	I
P/E	0.3897	ambiguous	0.3976	ambiguous	-0.396	Destabilizing	0.002	N	0.145	neutral	None	None	None	None	I
P/F	0.6472	likely_pathogenic	0.6294	pathogenic	-0.881	Destabilizing	0.724	D	0.439	neutral	None	None	None	None	I
P/G	0.5966	likely_pathogenic	0.6009	pathogenic	-0.691	Destabilizing	0.428	N	0.36	neutral	None	None	None	None	I
P/H	0.2978	likely_benign	0.3015	benign	-0.259	Destabilizing	0.8	D	0.299	neutral	N	0.482089526	None	None	I
P/I	0.1925	likely_benign	0.2147	benign	-0.398	Destabilizing	0.272	N	0.407	neutral	None	None	None	None	I
P/K	0.181	likely_benign	0.1893	benign	-0.287	Destabilizing	0.001	N	0.09	neutral	None	None	None	None	I
P/L	0.1317	likely_benign	0.1249	benign	-0.398	Destabilizing	0.001	N	0.171	neutral	N	0.47268501	None	None	I
P/M	0.293	likely_benign	0.3043	benign	-0.264	Destabilizing	0.724	D	0.337	neutral	None	None	None	None	I
P/N	0.5737	likely_pathogenic	0.5883	pathogenic	-0.038	Destabilizing	0.724	D	0.421	neutral	None	None	None	None	I
P/Q	0.1934	likely_benign	0.2044	benign	-0.345	Destabilizing	0.568	D	0.531	neutral	None	None	None	None	I
P/R	0.1493	likely_benign	0.1568	benign	0.24	Stabilizing	0.22	N	0.42	neutral	N	0.477765543	None	None	I
P/S	0.243	likely_benign	0.2601	benign	-0.434	Destabilizing	0.22	N	0.527	neutral	N	0.50520286	None	None	I
P/T	0.129	likely_benign	0.146	benign	-0.46	Destabilizing	0.361	N	0.478	neutral	N	0.512494192	None	None	I
P/V	0.1407	likely_benign	0.1555	benign	-0.42	Destabilizing	0.272	N	0.401	neutral	None	None	None	None	I
P/W	0.8379	likely_pathogenic	0.8221	pathogenic	-0.913	Destabilizing	0.984	D	0.458	neutral	None	None	None	None	I
P/Y	0.6053	likely_pathogenic	0.6003	pathogenic	-0.591	Destabilizing	0.942	D	0.427	neutral	None	None	None	None	I

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.