TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21262	64009;64010;64011	chr2:178587525;178587524;178587523	chr2:179452252;179452251;179452250
N2AB	19621	59086;59087;59088	chr2:178587525;178587524;178587523	chr2:179452252;179452251;179452250
N2A	18694	56305;56306;56307	chr2:178587525;178587524;178587523	chr2:179452252;179452251;179452250
N2B	12197	36814;36815;36816	chr2:178587525;178587524;178587523	chr2:179452252;179452251;179452250
Novex-1	12322	37189;37190;37191	chr2:178587525;178587524;178587523	chr2:179452252;179452251;179452250
Novex-2	12389	37390;37391;37392	chr2:178587525;178587524;178587523	chr2:179452252;179452251;179452250
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-123
• Domain position: 86
• Structural Position: 175
• Q(SASA): 0.471
• 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
R/G	None	None	0.117	N	0.473	0.307	0.43923137753	gnomAD-4.0.0	1.60277E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87829E-06	0	0
R/T	rs1342165359	-0.254	0.117	N	0.448	0.145	0.331365685468	gnomAD-2.1.1	4.09E-06	None	None	None	None	I	None	0	2.95E-05	None	0	0	None	0	None	0	0	0
R/T	rs1342165359	-0.254	0.117	N	0.448	0.145	0.331365685468	gnomAD-4.0.0	1.60321E-06	None	None	None	None	I	None	0	2.31471E-05	None	0	0	None	0	0	0	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
R/A	0.5838	likely_pathogenic	0.6717	pathogenic	-0.625	Destabilizing	0.035	N	0.45	neutral	None	None	None	None	I
R/C	0.3053	likely_benign	0.3669	ambiguous	-0.717	Destabilizing	0.935	D	0.537	neutral	None	None	None	None	I
R/D	0.8393	likely_pathogenic	0.8692	pathogenic	0.12	Stabilizing	0.149	N	0.449	neutral	None	None	None	None	I
R/E	0.5301	ambiguous	0.5891	pathogenic	0.25	Stabilizing	0.035	N	0.44	neutral	None	None	None	None	I
R/F	0.811	likely_pathogenic	0.8529	pathogenic	-0.533	Destabilizing	0.791	D	0.522	neutral	None	None	None	None	I
R/G	0.5887	likely_pathogenic	0.6786	pathogenic	-0.913	Destabilizing	0.117	N	0.473	neutral	N	0.499531077	None	None	I
R/H	0.149	likely_benign	0.1667	benign	-1.218	Destabilizing	0.555	D	0.441	neutral	None	None	None	None	I
R/I	0.4385	ambiguous	0.48	ambiguous	0.137	Stabilizing	0.484	N	0.523	neutral	D	0.526920219	None	None	I
R/K	0.0797	likely_benign	0.1001	benign	-0.49	Destabilizing	None	N	0.131	neutral	N	0.429852245	None	None	I
R/L	0.3697	ambiguous	0.4282	ambiguous	0.137	Stabilizing	0.149	N	0.473	neutral	None	None	None	None	I
R/M	0.3832	ambiguous	0.4461	ambiguous	-0.342	Destabilizing	0.791	D	0.445	neutral	None	None	None	None	I
R/N	0.6998	likely_pathogenic	0.7654	pathogenic	-0.21	Destabilizing	0.149	N	0.436	neutral	None	None	None	None	I
R/P	0.9658	likely_pathogenic	0.9767	pathogenic	-0.096	Destabilizing	0.555	D	0.463	neutral	None	None	None	None	I
R/Q	0.1301	likely_benign	0.1456	benign	-0.295	Destabilizing	0.081	N	0.487	neutral	None	None	None	None	I
R/S	0.6618	likely_pathogenic	0.7313	pathogenic	-0.924	Destabilizing	0.062	N	0.46	neutral	N	0.520127532	None	None	I
R/T	0.3443	ambiguous	0.4143	ambiguous	-0.609	Destabilizing	0.117	N	0.448	neutral	N	0.50365657	None	None	I
R/V	0.4801	ambiguous	0.5403	ambiguous	-0.096	Destabilizing	0.38	N	0.465	neutral	None	None	None	None	I
R/W	0.4183	ambiguous	0.4708	ambiguous	-0.298	Destabilizing	0.935	D	0.607	neutral	None	None	None	None	I
R/Y	0.6673	likely_pathogenic	0.7237	pathogenic	0.024	Stabilizing	0.791	D	0.506	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.