TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17627	53104;53105;53106	chr2:178607908;178607907;178607906	chr2:179472635;179472634;179472633
N2AB	15986	48181;48182;48183	chr2:178607908;178607907;178607906	chr2:179472635;179472634;179472633
N2A	15059	45400;45401;45402	chr2:178607908;178607907;178607906	chr2:179472635;179472634;179472633
N2B	8562	25909;25910;25911	chr2:178607908;178607907;178607906	chr2:179472635;179472634;179472633
Novex-1	8687	26284;26285;26286	chr2:178607908;178607907;178607906	chr2:179472635;179472634;179472633
Novex-2	8754	26485;26486;26487	chr2:178607908;178607907;178607906	chr2:179472635;179472634;179472633
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-16
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.3929
• 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
R/C	rs767433978	-0.816	1.0	N	0.707	0.319	0.504235531984	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	8.88E-06	0
R/C	rs767433978	-0.816	1.0	N	0.707	0.319	0.504235531984	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
R/C	rs767433978	-0.816	1.0	N	0.707	0.319	0.504235531984	gnomAD-4.0.0	4.34014E-06	None	None	None	None	N	None	4.00898E-05	0	None	0	2.23594E-05	None	0	0	2.5438E-06	0	0
R/G	None	None	0.988	N	0.587	0.34	0.512883945787	gnomAD-4.0.0	6.84474E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99755E-07	0	0
R/H	rs536494011	-1.296	1.0	N	0.628	0.299	0.17948927462	gnomAD-2.1.1	5.36E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	4E-05	1.0157E-04	0
R/H	rs536494011	-1.296	1.0	N	0.628	0.299	0.17948927462	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	4.42E-05	0	0
R/H	rs536494011	-1.296	1.0	N	0.628	0.299	0.17948927462	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/H	rs536494011	-1.296	1.0	N	0.628	0.299	0.17948927462	gnomAD-4.0.0	3.3478E-05	None	None	None	None	N	None	2.66773E-05	3.33567E-05	None	0	0	None	1.5627E-05	0	3.56141E-05	2.19616E-05	8.0082E-05

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
R/A	0.5903	likely_pathogenic	0.4528	ambiguous	-0.918	Destabilizing	0.86	D	0.563	neutral	None	None	None	None	N
R/C	0.1458	likely_benign	0.1126	benign	-1.078	Destabilizing	1.0	D	0.707	prob.neutral	N	0.456075188	None	None	N
R/D	0.8432	likely_pathogenic	0.7408	pathogenic	-0.832	Destabilizing	0.993	D	0.691	prob.neutral	None	None	None	None	N
R/E	0.5629	ambiguous	0.4399	ambiguous	-0.633	Destabilizing	0.926	D	0.567	neutral	None	None	None	None	N
R/F	0.7538	likely_pathogenic	0.6134	pathogenic	-0.323	Destabilizing	0.915	D	0.717	prob.delet.	None	None	None	None	N
R/G	0.3719	ambiguous	0.2514	benign	-1.257	Destabilizing	0.988	D	0.587	neutral	N	0.478431178	None	None	N
R/H	0.1397	likely_benign	0.1112	benign	-1.391	Destabilizing	1.0	D	0.628	neutral	N	0.501962193	None	None	N
R/I	0.5958	likely_pathogenic	0.4492	ambiguous	0.03	Stabilizing	0.915	D	0.663	neutral	None	None	None	None	N
R/K	0.1399	likely_benign	0.1094	benign	-0.775	Destabilizing	0.837	D	0.536	neutral	None	None	None	None	N
R/L	0.3109	likely_benign	0.1966	benign	0.03	Stabilizing	0.036	N	0.46	neutral	N	0.431464745	None	None	N
R/M	0.467	ambiguous	0.3467	ambiguous	-0.633	Destabilizing	0.956	D	0.668	neutral	None	None	None	None	N
R/N	0.6297	likely_pathogenic	0.5261	ambiguous	-0.993	Destabilizing	0.993	D	0.615	neutral	None	None	None	None	N
R/P	0.4836	ambiguous	0.3555	ambiguous	-0.27	Destabilizing	0.996	D	0.676	prob.neutral	N	0.471081926	None	None	N
R/Q	0.1293	likely_benign	0.1028	benign	-0.845	Destabilizing	0.993	D	0.616	neutral	None	None	None	None	N
R/S	0.6601	likely_pathogenic	0.5192	ambiguous	-1.482	Destabilizing	0.988	D	0.611	neutral	N	0.486011306	None	None	N
R/T	0.3281	likely_benign	0.2281	benign	-1.081	Destabilizing	0.86	D	0.602	neutral	None	None	None	None	N
R/V	0.6295	likely_pathogenic	0.4805	ambiguous	-0.27	Destabilizing	0.754	D	0.625	neutral	None	None	None	None	N
R/W	0.3219	likely_benign	0.2297	benign	-0.087	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
R/Y	0.5586	ambiguous	0.4219	ambiguous	0.113	Stabilizing	0.978	D	0.677	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.