TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22146	66661;66662;66663	chr2:178581933;178581932;178581931	chr2:179446660;179446659;179446658
N2AB	20505	61738;61739;61740	chr2:178581933;178581932;178581931	chr2:179446660;179446659;179446658
N2A	19578	58957;58958;58959	chr2:178581933;178581932;178581931	chr2:179446660;179446659;179446658
N2B	13081	39466;39467;39468	chr2:178581933;178581932;178581931	chr2:179446660;179446659;179446658
Novex-1	13206	39841;39842;39843	chr2:178581933;178581932;178581931	chr2:179446660;179446659;179446658
Novex-2	13273	40042;40043;40044	chr2:178581933;178581932;178581931	chr2:179446660;179446659;179446658
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: Fn3-48
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.8886
• 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/E	rs2047865333	None	0.688	N	0.498	0.228	0.198526703765	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/E	rs2047865333	None	0.688	N	0.498	0.228	0.198526703765	gnomAD-4.0.0	6.57333E-06	None	None	None	None	I	None	2.4122E-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	0.1983	likely_benign	0.2196	benign	0.036	Stabilizing	0.594	D	0.456	neutral	None	None	None	None	I
K/C	0.6856	likely_pathogenic	0.6915	pathogenic	-0.364	Destabilizing	0.998	D	0.502	neutral	None	None	None	None	I
K/D	0.4112	ambiguous	0.4375	ambiguous	-0.138	Destabilizing	0.78	D	0.456	neutral	None	None	None	None	I
K/E	0.1335	likely_benign	0.1496	benign	-0.145	Destabilizing	0.688	D	0.498	neutral	N	0.395571021	None	None	I
K/F	0.6809	likely_pathogenic	0.7135	pathogenic	-0.264	Destabilizing	0.994	D	0.509	neutral	None	None	None	None	I
K/G	0.369	ambiguous	0.3981	ambiguous	-0.111	Destabilizing	0.745	D	0.476	neutral	None	None	None	None	I
K/H	0.3178	likely_benign	0.3304	benign	-0.243	Destabilizing	0.981	D	0.461	neutral	None	None	None	None	I
K/I	0.2612	likely_benign	0.2804	benign	0.34	Stabilizing	0.981	D	0.545	neutral	None	None	None	None	I
K/L	0.2645	likely_benign	0.2817	benign	0.34	Stabilizing	0.935	D	0.531	neutral	None	None	None	None	I
K/M	0.2112	likely_benign	0.2334	benign	-0.006	Destabilizing	0.998	D	0.456	neutral	N	0.505605505	None	None	I
K/N	0.3248	likely_benign	0.3479	ambiguous	0.102	Stabilizing	0.067	N	0.237	neutral	N	0.418274522	None	None	I
K/P	0.3123	likely_benign	0.3117	benign	0.263	Stabilizing	0.981	D	0.512	neutral	None	None	None	None	I
K/Q	0.1234	likely_benign	0.1297	benign	-0.044	Destabilizing	0.915	D	0.522	neutral	N	0.444653047	None	None	I
K/R	0.09	likely_benign	0.0916	benign	-0.058	Destabilizing	0.915	D	0.483	neutral	N	0.44430633	None	None	I
K/S	0.2851	likely_benign	0.3139	benign	-0.297	Destabilizing	0.104	N	0.144	neutral	None	None	None	None	I
K/T	0.1344	likely_benign	0.1531	benign	-0.178	Destabilizing	0.728	D	0.421	neutral	N	0.415906221	None	None	I
K/V	0.2042	likely_benign	0.2195	benign	0.263	Stabilizing	0.935	D	0.534	neutral	None	None	None	None	I
K/W	0.7826	likely_pathogenic	0.7984	pathogenic	-0.348	Destabilizing	0.998	D	0.592	neutral	None	None	None	None	I
K/Y	0.6011	likely_pathogenic	0.6199	pathogenic	0.009	Stabilizing	0.994	D	0.559	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.