TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26972	81139;81140;81141	chr2:178565218;178565217;178565216	chr2:179429945;179429944;179429943
N2AB	25331	76216;76217;76218	chr2:178565218;178565217;178565216	chr2:179429945;179429944;179429943
N2A	24404	73435;73436;73437	chr2:178565218;178565217;178565216	chr2:179429945;179429944;179429943
N2B	17907	53944;53945;53946	chr2:178565218;178565217;178565216	chr2:179429945;179429944;179429943
Novex-1	18032	54319;54320;54321	chr2:178565218;178565217;178565216	chr2:179429945;179429944;179429943
Novex-2	18099	54520;54521;54522	chr2:178565218;178565217;178565216	chr2:179429945;179429944;179429943
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-84
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5901
• 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
K/R	rs1705272007	None	0.027	N	0.243	0.082	0.222439326576	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1705272007	None	0.027	N	0.243	0.082	0.222439326576	gnomAD-4.0.0	6.57358E-06	None	None	None	None	I	None	2.41289E-05	0	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
K/A	0.6805	likely_pathogenic	0.6941	pathogenic	-0.217	Destabilizing	0.717	D	0.534	neutral	None	None	None	None	I
K/C	0.8479	likely_pathogenic	0.8426	pathogenic	-0.391	Destabilizing	0.998	D	0.898	deleterious	None	None	None	None	I
K/D	0.9378	likely_pathogenic	0.9404	pathogenic	0.383	Stabilizing	0.973	D	0.625	neutral	None	None	None	None	I
K/E	0.5618	ambiguous	0.5969	pathogenic	0.414	Stabilizing	0.792	D	0.499	neutral	N	0.487318722	None	None	I
K/F	0.9462	likely_pathogenic	0.9486	pathogenic	-0.317	Destabilizing	0.947	D	0.881	deleterious	None	None	None	None	I
K/G	0.8544	likely_pathogenic	0.855	pathogenic	-0.454	Destabilizing	0.973	D	0.539	neutral	None	None	None	None	I
K/H	0.6288	likely_pathogenic	0.6106	pathogenic	-0.713	Destabilizing	0.993	D	0.609	neutral	None	None	None	None	I
K/I	0.539	ambiguous	0.5828	pathogenic	0.337	Stabilizing	0.899	D	0.608	neutral	None	None	None	None	I
K/L	0.675	likely_pathogenic	0.6793	pathogenic	0.337	Stabilizing	0.717	D	0.551	neutral	None	None	None	None	I
K/M	0.4311	ambiguous	0.4603	ambiguous	0.204	Stabilizing	0.99	D	0.615	neutral	N	0.494409066	None	None	I
K/N	0.7787	likely_pathogenic	0.7919	pathogenic	0.112	Stabilizing	0.931	D	0.636	neutral	N	0.487825701	None	None	I
K/P	0.7189	likely_pathogenic	0.7302	pathogenic	0.182	Stabilizing	0.991	D	0.679	prob.neutral	None	None	None	None	I
K/Q	0.3014	likely_benign	0.2953	benign	-0.071	Destabilizing	0.931	D	0.676	prob.neutral	N	0.494409066	None	None	I
K/R	0.1161	likely_benign	0.1111	benign	-0.09	Destabilizing	0.027	N	0.243	neutral	N	0.475428953	None	None	I
K/S	0.8143	likely_pathogenic	0.8095	pathogenic	-0.543	Destabilizing	0.835	D	0.632	neutral	None	None	None	None	I
K/T	0.4815	ambiguous	0.4957	ambiguous	-0.341	Destabilizing	0.792	D	0.613	neutral	N	0.459161608	None	None	I
K/V	0.5392	ambiguous	0.5636	ambiguous	0.182	Stabilizing	0.035	N	0.425	neutral	None	None	None	None	I
K/W	0.9544	likely_pathogenic	0.9527	pathogenic	-0.226	Destabilizing	0.998	D	0.903	deleterious	None	None	None	None	I
K/Y	0.8603	likely_pathogenic	0.8611	pathogenic	0.107	Stabilizing	0.973	D	0.895	deleterious	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.