TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26480	79663;79664;79665	chr2:178566694;178566693;178566692	chr2:179431421;179431420;179431419
N2AB	24839	74740;74741;74742	chr2:178566694;178566693;178566692	chr2:179431421;179431420;179431419
N2A	23912	71959;71960;71961	chr2:178566694;178566693;178566692	chr2:179431421;179431420;179431419
N2B	17415	52468;52469;52470	chr2:178566694;178566693;178566692	chr2:179431421;179431420;179431419
Novex-1	17540	52843;52844;52845	chr2:178566694;178566693;178566692	chr2:179431421;179431420;179431419
Novex-2	17607	53044;53045;53046	chr2:178566694;178566693;178566692	chr2:179431421;179431420;179431419
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-80
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.2968
• 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
K/N	None	None	0.997	N	0.635	0.249	0.144782658237	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
K/A	0.6782	likely_pathogenic	0.6205	pathogenic	-0.336	Destabilizing	0.987	D	0.542	neutral	None	None	None	None	N
K/C	0.8145	likely_pathogenic	0.7594	pathogenic	-0.364	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/D	0.9418	likely_pathogenic	0.9235	pathogenic	-0.151	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	N
K/E	0.5257	ambiguous	0.4609	ambiguous	-0.097	Destabilizing	0.991	D	0.538	neutral	N	0.520438885	None	None	N
K/F	0.9067	likely_pathogenic	0.8882	pathogenic	-0.247	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
K/G	0.8559	likely_pathogenic	0.8138	pathogenic	-0.641	Destabilizing	0.993	D	0.619	neutral	None	None	None	None	N
K/H	0.4648	ambiguous	0.4144	ambiguous	-0.991	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
K/I	0.5595	ambiguous	0.5425	ambiguous	0.423	Stabilizing	0.999	D	0.779	deleterious	N	0.489769261	None	None	N
K/L	0.5355	ambiguous	0.5144	ambiguous	0.423	Stabilizing	0.999	D	0.558	neutral	None	None	None	None	N
K/M	0.4285	ambiguous	0.4042	ambiguous	0.371	Stabilizing	1.0	D	0.684	prob.delet.	None	None	None	None	N
K/N	0.8371	likely_pathogenic	0.8055	pathogenic	-0.2	Destabilizing	0.997	D	0.635	neutral	N	0.492961624	None	None	N
K/P	0.8729	likely_pathogenic	0.8432	pathogenic	0.201	Stabilizing	0.999	D	0.69	prob.delet.	None	None	None	None	N
K/Q	0.2414	likely_benign	0.2096	benign	-0.376	Destabilizing	0.999	D	0.627	neutral	N	0.518014655	None	None	N
K/R	0.0837	likely_benign	0.0789	benign	-0.408	Destabilizing	0.996	D	0.634	neutral	N	0.470434139	None	None	N
K/S	0.8042	likely_pathogenic	0.7602	pathogenic	-0.787	Destabilizing	0.854	D	0.416	neutral	None	None	None	None	N
K/T	0.394	ambiguous	0.3706	ambiguous	-0.553	Destabilizing	0.983	D	0.66	prob.neutral	N	0.454184102	None	None	N
K/V	0.4938	ambiguous	0.4747	ambiguous	0.201	Stabilizing	0.999	D	0.652	prob.neutral	None	None	None	None	N
K/W	0.8751	likely_pathogenic	0.8449	pathogenic	-0.145	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
K/Y	0.8302	likely_pathogenic	0.7955	pathogenic	0.157	Stabilizing	1.0	D	0.779	deleterious	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.