TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28291	85096;85097;85098	chr2:178561261;178561260;178561259	chr2:179425988;179425987;179425986
N2AB	26650	80173;80174;80175	chr2:178561261;178561260;178561259	chr2:179425988;179425987;179425986
N2A	25723	77392;77393;77394	chr2:178561261;178561260;178561259	chr2:179425988;179425987;179425986
N2B	19226	57901;57902;57903	chr2:178561261;178561260;178561259	chr2:179425988;179425987;179425986
Novex-1	19351	58276;58277;58278	chr2:178561261;178561260;178561259	chr2:179425988;179425987;179425986
Novex-2	19418	58477;58478;58479	chr2:178561261;178561260;178561259	chr2:179425988;179425987;179425986
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: Fn3-94
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.164
• 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	rs192152102	-2.004	1.0	N	0.787	0.344	None	gnomAD-2.1.1	7.14276E-04	None	None	None	None	N	None	0	0	None	0	0	None	2.61421E-04	None	2.00096E-03	1.00027E-03	1.96685E-03
R/C	rs192152102	-2.004	1.0	N	0.787	0.344	None	gnomAD-3.1.2	4.34033E-04	None	None	None	None	N	None	0	0	0	0	0	None	1.97927E-03	0	6.47078E-04	0	4.79386E-04
R/C	rs192152102	-2.004	1.0	N	0.787	0.344	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	0	2E-03	None	None	None	0	None
R/C	rs192152102	-2.004	1.0	N	0.787	0.344	None	gnomAD-4.0.0	5.85006E-04	None	None	None	None	N	None	3.99989E-05	1.66639E-05	None	0	0	None	2.2991E-03	3.29924E-04	6.17913E-04	1.53725E-04	7.6827E-04
R/H	rs774924903	-2.024	0.159	N	0.447	0.175	0.188950314367	gnomAD-2.1.1	3.21E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	3.27E-05	None	0	5.47E-05	0
R/H	rs774924903	-2.024	0.159	N	0.447	0.175	0.188950314367	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
R/H	rs774924903	-2.024	0.159	N	0.447	0.175	0.188950314367	gnomAD-4.0.0	3.40863E-05	None	None	None	None	N	None	2.67037E-05	0	None	0	2.23105E-05	None	0	0	4.06852E-05	2.19587E-05	3.20215E-05
R/S	None	None	0.96	N	0.651	0.337	0.317084106153	gnomAD-4.0.0	6.84238E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99452E-07	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
R/A	0.8114	likely_pathogenic	0.786	pathogenic	-2.221	Highly Destabilizing	0.86	D	0.653	neutral	None	None	None	None	N
R/C	0.2495	likely_benign	0.2396	benign	-2.126	Highly Destabilizing	1.0	D	0.787	deleterious	N	0.479024879	None	None	N
R/D	0.9791	likely_pathogenic	0.9755	pathogenic	-1.62	Destabilizing	0.978	D	0.74	deleterious	None	None	None	None	N
R/E	0.8165	likely_pathogenic	0.8097	pathogenic	-1.36	Destabilizing	0.86	D	0.63	neutral	None	None	None	None	N
R/F	0.8061	likely_pathogenic	0.7888	pathogenic	-1.255	Destabilizing	0.915	D	0.766	deleterious	None	None	None	None	N
R/G	0.7105	likely_pathogenic	0.7086	pathogenic	-2.595	Highly Destabilizing	0.96	D	0.696	prob.neutral	N	0.475229898	None	None	N
R/H	0.1947	likely_benign	0.1948	benign	-1.841	Destabilizing	0.159	N	0.447	neutral	N	0.472013895	None	None	N
R/I	0.6715	likely_pathogenic	0.6574	pathogenic	-1.106	Destabilizing	0.956	D	0.773	deleterious	None	None	None	None	N
R/K	0.1473	likely_benign	0.1372	benign	-1.171	Destabilizing	0.926	D	0.629	neutral	None	None	None	None	N
R/L	0.5598	ambiguous	0.5471	ambiguous	-1.106	Destabilizing	0.855	D	0.697	prob.neutral	N	0.4785179	None	None	N
R/M	0.5433	ambiguous	0.5342	ambiguous	-1.572	Destabilizing	0.998	D	0.7	prob.neutral	None	None	None	None	N
R/N	0.9223	likely_pathogenic	0.9116	pathogenic	-1.84	Destabilizing	0.86	D	0.642	neutral	None	None	None	None	N
R/P	0.995	likely_pathogenic	0.9949	pathogenic	-1.471	Destabilizing	0.996	D	0.747	deleterious	N	0.508564799	None	None	N
R/Q	0.1859	likely_benign	0.1828	benign	-1.612	Destabilizing	0.978	D	0.66	neutral	None	None	None	None	N
R/S	0.8659	likely_pathogenic	0.8424	pathogenic	-2.687	Highly Destabilizing	0.96	D	0.651	neutral	N	0.466329128	None	None	N
R/T	0.7689	likely_pathogenic	0.7508	pathogenic	-2.19	Highly Destabilizing	0.978	D	0.666	neutral	None	None	None	None	N
R/V	0.7242	likely_pathogenic	0.7092	pathogenic	-1.471	Destabilizing	0.956	D	0.754	deleterious	None	None	None	None	N
R/W	0.3966	ambiguous	0.3916	ambiguous	-0.716	Destabilizing	0.994	D	0.785	deleterious	None	None	None	None	N
R/Y	0.5415	ambiguous	0.5205	ambiguous	-0.676	Destabilizing	0.019	N	0.595	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.