TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8633	26122;26123;26124	chr2:178715517;178715516;178715515	chr2:179580244;179580243;179580242
N2AB	8316	25171;25172;25173	chr2:178715517;178715516;178715515	chr2:179580244;179580243;179580242
N2A	7389	22390;22391;22392	chr2:178715517;178715516;178715515	chr2:179580244;179580243;179580242
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-71
• Domain position: 85
• Structural Position: 169
• Q(SASA): 0.1495
• 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/G	rs776980958	-1.412	0.606	N	0.501	0.164	0.21279746466	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
S/G	rs776980958	-1.412	0.606	N	0.501	0.164	0.21279746466	gnomAD-4.0.0	1.59484E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86788E-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	0.1236	likely_benign	0.103	benign	-0.926	Destabilizing	0.017	N	0.365	neutral	None	None	None	None	N
S/C	0.0882	likely_benign	0.0746	benign	-0.493	Destabilizing	0.001	N	0.398	neutral	N	0.417965957	None	None	N
S/D	0.9058	likely_pathogenic	0.8586	pathogenic	-0.109	Destabilizing	0.727	D	0.553	neutral	None	None	None	None	N
S/E	0.9522	likely_pathogenic	0.9269	pathogenic	-0.08	Destabilizing	0.789	D	0.561	neutral	None	None	None	None	N
S/F	0.4797	ambiguous	0.389	ambiguous	-1.035	Destabilizing	0.986	D	0.729	prob.delet.	None	None	None	None	N
S/G	0.1932	likely_benign	0.1525	benign	-1.208	Destabilizing	0.606	D	0.501	neutral	N	0.520207677	None	None	N
S/H	0.7844	likely_pathogenic	0.7106	pathogenic	-1.576	Destabilizing	0.995	D	0.675	prob.neutral	None	None	None	None	N
S/I	0.3372	likely_benign	0.275	benign	-0.269	Destabilizing	0.883	D	0.665	neutral	N	0.488467941	None	None	N
S/K	0.9838	likely_pathogenic	0.9726	pathogenic	-0.551	Destabilizing	0.909	D	0.548	neutral	None	None	None	None	N
S/L	0.2149	likely_benign	0.1742	benign	-0.269	Destabilizing	0.673	D	0.648	neutral	None	None	None	None	N
S/M	0.3821	ambiguous	0.3172	benign	0.035	Stabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	N
S/N	0.452	ambiguous	0.3631	ambiguous	-0.574	Destabilizing	0.191	N	0.557	neutral	N	0.488467941	None	None	N
S/P	0.9623	likely_pathogenic	0.9471	pathogenic	-0.454	Destabilizing	0.844	D	0.717	prob.delet.	None	None	None	None	N
S/Q	0.9101	likely_pathogenic	0.8768	pathogenic	-0.67	Destabilizing	0.986	D	0.668	neutral	None	None	None	None	N
S/R	0.9616	likely_pathogenic	0.9378	pathogenic	-0.52	Destabilizing	0.982	D	0.733	prob.delet.	D	0.524536061	None	None	N
S/T	0.0918	likely_benign	0.0793	benign	-0.625	Destabilizing	None	N	0.195	neutral	N	0.467199911	None	None	N
S/V	0.295	likely_benign	0.2405	benign	-0.454	Destabilizing	0.435	N	0.65	neutral	None	None	None	None	N
S/W	0.7518	likely_pathogenic	0.6699	pathogenic	-0.975	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
S/Y	0.4694	ambiguous	0.3765	ambiguous	-0.711	Destabilizing	0.995	D	0.723	prob.delet.	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.