TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26399	79420;79421;79422	chr2:178566937;178566936;178566935	chr2:179431664;179431663;179431662
N2AB	24758	74497;74498;74499	chr2:178566937;178566936;178566935	chr2:179431664;179431663;179431662
N2A	23831	71716;71717;71718	chr2:178566937;178566936;178566935	chr2:179431664;179431663;179431662
N2B	17334	52225;52226;52227	chr2:178566937;178566936;178566935	chr2:179431664;179431663;179431662
Novex-1	17459	52600;52601;52602	chr2:178566937;178566936;178566935	chr2:179431664;179431663;179431662
Novex-2	17526	52801;52802;52803	chr2:178566937;178566936;178566935	chr2:179431664;179431663;179431662
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: Fn3-80
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2422
• 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/V	None	None	0.379	N	0.293	0.301	0.247322355667	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4393	ambiguous	0.3927	ambiguous	-0.991	Destabilizing	0.992	D	0.361	neutral	None	None	None	None	N
A/D	0.767	likely_pathogenic	0.7386	pathogenic	-2.014	Highly Destabilizing	0.549	D	0.401	neutral	N	0.417354589	None	None	N
A/E	0.7168	likely_pathogenic	0.6865	pathogenic	-2.086	Highly Destabilizing	0.617	D	0.383	neutral	None	None	None	None	N
A/F	0.5999	likely_pathogenic	0.5518	ambiguous	-1.388	Destabilizing	0.92	D	0.435	neutral	None	None	None	None	N
A/G	0.1777	likely_benign	0.156	benign	-1.24	Destabilizing	0.002	N	0.073	neutral	N	0.417698519	None	None	N
A/H	0.707	likely_pathogenic	0.7165	pathogenic	-1.384	Destabilizing	0.972	D	0.407	neutral	None	None	None	None	N
A/I	0.5235	ambiguous	0.4467	ambiguous	-0.645	Destabilizing	0.447	N	0.429	neutral	None	None	None	None	N
A/K	0.8314	likely_pathogenic	0.8177	pathogenic	-1.333	Destabilizing	0.617	D	0.391	neutral	None	None	None	None	N
A/L	0.2754	likely_benign	0.2484	benign	-0.645	Destabilizing	0.447	N	0.373	neutral	None	None	None	None	N
A/M	0.2991	likely_benign	0.2461	benign	-0.328	Destabilizing	0.92	D	0.383	neutral	None	None	None	None	N
A/N	0.4038	ambiguous	0.384	ambiguous	-1.088	Destabilizing	0.617	D	0.393	neutral	None	None	None	None	N
A/P	0.9238	likely_pathogenic	0.9015	pathogenic	-0.74	Destabilizing	0.712	D	0.427	neutral	N	0.497586242	None	None	N
A/Q	0.5563	ambiguous	0.5473	ambiguous	-1.372	Destabilizing	0.85	D	0.394	neutral	None	None	None	None	N
A/R	0.7565	likely_pathogenic	0.7426	pathogenic	-0.841	Destabilizing	0.85	D	0.42	neutral	None	None	None	None	N
A/S	0.0981	likely_benign	0.0939	benign	-1.294	Destabilizing	0.007	N	0.064	neutral	N	0.385663458	None	None	N
A/T	0.0846	likely_benign	0.0763	benign	-1.299	Destabilizing	0.001	N	0.059	neutral	N	0.308856113	None	None	N
A/V	0.2589	likely_benign	0.2099	benign	-0.74	Destabilizing	0.379	N	0.293	neutral	N	0.447042778	None	None	N
A/W	0.9227	likely_pathogenic	0.9093	pathogenic	-1.686	Destabilizing	0.992	D	0.473	neutral	None	None	None	None	N
A/Y	0.7474	likely_pathogenic	0.7165	pathogenic	-1.327	Destabilizing	0.972	D	0.429	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.