TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28657	86194;86195;86196	chr2:178560163;178560162;178560161	chr2:179424890;179424889;179424888
N2AB	27016	81271;81272;81273	chr2:178560163;178560162;178560161	chr2:179424890;179424889;179424888
N2A	26089	78490;78491;78492	chr2:178560163;178560162;178560161	chr2:179424890;179424889;179424888
N2B	19592	58999;59000;59001	chr2:178560163;178560162;178560161	chr2:179424890;179424889;179424888
Novex-1	19717	59374;59375;59376	chr2:178560163;178560162;178560161	chr2:179424890;179424889;179424888
Novex-2	19784	59575;59576;59577	chr2:178560163;178560162;178560161	chr2:179424890;179424889;179424888
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: Fn3-97
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.4308
• 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/T	rs1423891310	0.065	0.892	N	0.553	0.215	0.369867359543	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/T	rs1423891310	0.065	0.892	N	0.553	0.215	0.369867359543	gnomAD-4.0.0	1.0948E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43923E-05	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	0.53	ambiguous	0.4766	ambiguous	-0.346	Destabilizing	0.916	D	0.51	neutral	None	None	None	None	N
K/C	0.7429	likely_pathogenic	0.6951	pathogenic	-0.334	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
K/D	0.7948	likely_pathogenic	0.7917	pathogenic	-0.151	Destabilizing	0.95	D	0.563	neutral	None	None	None	None	N
K/E	0.3884	ambiguous	0.3972	ambiguous	-0.134	Destabilizing	0.892	D	0.469	neutral	N	0.498796963	None	None	N
K/F	0.8451	likely_pathogenic	0.8151	pathogenic	-0.589	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
K/G	0.6759	likely_pathogenic	0.6385	pathogenic	-0.589	Destabilizing	0.845	D	0.535	neutral	None	None	None	None	N
K/H	0.4173	ambiguous	0.3967	ambiguous	-1.103	Destabilizing	0.987	D	0.619	neutral	None	None	None	None	N
K/I	0.5005	ambiguous	0.4498	ambiguous	0.228	Stabilizing	0.983	D	0.708	prob.delet.	N	0.473330568	None	None	N
K/L	0.5028	ambiguous	0.4488	ambiguous	0.228	Stabilizing	0.975	D	0.533	neutral	None	None	None	None	N
K/M	0.3759	ambiguous	0.3519	ambiguous	0.398	Stabilizing	0.999	D	0.589	neutral	None	None	None	None	N
K/N	0.6388	likely_pathogenic	0.6269	pathogenic	0.008	Stabilizing	0.056	N	0.247	neutral	N	0.453731103	None	None	N
K/P	0.779	likely_pathogenic	0.6644	pathogenic	0.065	Stabilizing	0.996	D	0.641	neutral	None	None	None	None	N
K/Q	0.2126	likely_benign	0.2079	benign	-0.294	Destabilizing	0.967	D	0.531	neutral	N	0.496642092	None	None	N
K/R	0.0931	likely_benign	0.0862	benign	-0.221	Destabilizing	0.025	N	0.28	neutral	N	0.467724694	None	None	N
K/S	0.61	likely_pathogenic	0.5758	pathogenic	-0.589	Destabilizing	0.845	D	0.463	neutral	None	None	None	None	N
K/T	0.3551	ambiguous	0.3227	benign	-0.41	Destabilizing	0.892	D	0.553	neutral	N	0.490332195	None	None	N
K/V	0.4432	ambiguous	0.3957	ambiguous	0.065	Stabilizing	0.987	D	0.651	neutral	None	None	None	None	N
K/W	0.8602	likely_pathogenic	0.8241	pathogenic	-0.483	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/Y	0.7041	likely_pathogenic	0.6804	pathogenic	-0.119	Destabilizing	0.996	D	0.695	prob.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.