TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29293	88102;88103;88104	chr2:178557385;178557384;178557383	chr2:179422112;179422111;179422110
N2AB	27652	83179;83180;83181	chr2:178557385;178557384;178557383	chr2:179422112;179422111;179422110
N2A	26725	80398;80399;80400	chr2:178557385;178557384;178557383	chr2:179422112;179422111;179422110
N2B	20228	60907;60908;60909	chr2:178557385;178557384;178557383	chr2:179422112;179422111;179422110
Novex-1	20353	61282;61283;61284	chr2:178557385;178557384;178557383	chr2:179422112;179422111;179422110
Novex-2	20420	61483;61484;61485	chr2:178557385;178557384;178557383	chr2:179422112;179422111;179422110
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-101
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.8712
• 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
R/C	rs191482653	-0.197	1.0	N	0.797	0.464	None	gnomAD-2.1.1	1.92691E-03	None	None	None	None	I	None	0	0	None	0	2.60379E-02	None	1.63388E-04	None	0	1.63983E-04	8.41515E-04
R/C	rs191482653	-0.197	1.0	N	0.797	0.464	None	gnomAD-3.1.2	7.49389E-04	None	None	None	None	I	None	2.41E-05	6.55E-05	0	0	2.04633E-02	None	9.43E-05	0	4.41E-05	2.06868E-04	4.78469E-04
R/C	rs191482653	-0.197	1.0	N	0.797	0.464	None	1000 genomes	3.19489E-03	None	None	None	None	I	None	0	0	None	None	1.59E-02	0	None	None	None	0	None
R/C	rs191482653	-0.197	1.0	N	0.797	0.464	None	Sasaki (2020)	None	Other	comp het with A9980T, A19938T	None	None	I	Genetic analysis of 2 siblings with asymmetric facial and limb weakness; variant prioritisation; no validation	None	None	None	None	None	None	None	None	None	None	None
R/C	rs191482653	-0.197	1.0	N	0.797	0.464	None	gnomAD-4.0.0	6.71047E-04	None	None	None	None	I	None	2.66546E-05	1.66644E-05	None	0	1.87703E-02	None	3.1249E-05	3.30033E-04	8.89942E-05	2.08589E-04	1.76051E-03
R/H	rs202001776	-0.539	1.0	N	0.778	0.376	None	gnomAD-2.1.1	7.14E-05	None	None	None	None	I	None	4.95991E-04	5.65E-05	None	0	0	None	9.8E-05	None	0	2.34E-05	0
R/H	rs202001776	-0.539	1.0	N	0.778	0.376	None	gnomAD-3.1.2	1.57752E-04	None	None	None	None	I	None	4.82532E-04	1.30976E-04	0	0	0	None	0	0	1.47E-05	2.07211E-04	0
R/H	rs202001776	-0.539	1.0	N	0.778	0.376	None	gnomAD-4.0.0	3.90384E-05	None	None	None	None	I	None	3.60356E-04	6.66733E-05	None	0	0	None	0	0	1.52562E-05	1.20768E-04	4.80277E-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	0.4796	ambiguous	0.4598	ambiguous	0.011	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	I
R/C	0.1887	likely_benign	0.2135	benign	-0.272	Destabilizing	1.0	D	0.797	deleterious	N	0.478969789	None	None	I
R/D	0.69	likely_pathogenic	0.6654	pathogenic	-0.171	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
R/E	0.4904	ambiguous	0.4502	ambiguous	-0.114	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
R/F	0.7113	likely_pathogenic	0.7084	pathogenic	-0.229	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
R/G	0.2586	likely_benign	0.2733	benign	-0.164	Destabilizing	1.0	D	0.634	neutral	N	0.499490396	None	None	I
R/H	0.1109	likely_benign	0.1177	benign	-0.581	Destabilizing	1.0	D	0.778	deleterious	N	0.491028416	None	None	I
R/I	0.5563	ambiguous	0.5187	ambiguous	0.433	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
R/K	0.1216	likely_benign	0.1279	benign	-0.154	Destabilizing	0.998	D	0.572	neutral	None	None	None	None	I
R/L	0.3768	ambiguous	0.3746	ambiguous	0.433	Stabilizing	1.0	D	0.634	neutral	N	0.497626314	None	None	I
R/M	0.4761	ambiguous	0.4515	ambiguous	-0.038	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
R/N	0.5895	likely_pathogenic	0.5569	ambiguous	-0.035	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
R/P	0.3351	likely_benign	0.3357	benign	0.312	Stabilizing	1.0	D	0.742	deleterious	N	0.428246373	None	None	I
R/Q	0.1128	likely_benign	0.1176	benign	-0.094	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
R/S	0.5054	ambiguous	0.4899	ambiguous	-0.313	Destabilizing	1.0	D	0.702	prob.neutral	N	0.445215981	None	None	I
R/T	0.3387	likely_benign	0.3176	benign	-0.132	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
R/V	0.5739	likely_pathogenic	0.5534	ambiguous	0.312	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
R/W	0.2536	likely_benign	0.2768	benign	-0.329	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
R/Y	0.4929	ambiguous	0.4926	ambiguous	0.077	Stabilizing	1.0	D	0.763	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.