TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33154	99685;99686;99687	chr2:178537747;178537746;178537745	chr2:179402474;179402473;179402472
N2AB	31513	94762;94763;94764	chr2:178537747;178537746;178537745	chr2:179402474;179402473;179402472
N2A	30586	91981;91982;91983	chr2:178537747;178537746;178537745	chr2:179402474;179402473;179402472
N2B	24089	72490;72491;72492	chr2:178537747;178537746;178537745	chr2:179402474;179402473;179402472
Novex-1	24214	72865;72866;72867	chr2:178537747;178537746;178537745	chr2:179402474;179402473;179402472
Novex-2	24281	73066;73067;73068	chr2:178537747;178537746;178537745	chr2:179402474;179402473;179402472
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: Ig-156
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.5036
• 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	rs143556947	-0.652	1.0	N	0.711	0.486	None	gnomAD-2.1.1	3.21E-05	None	None	None	None	N	None	1.65385E-04	0	None	0	0	None	0	None	4E-05	3.12E-05	0
R/C	rs143556947	-0.652	1.0	N	0.711	0.486	None	gnomAD-3.1.2	9.21E-05	None	None	None	None	N	None	1.93171E-04	6.55E-05	0	0	0	None	0	0	7.35E-05	0	0
R/C	rs143556947	-0.652	1.0	N	0.711	0.486	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	0	3E-03	None	None	None	0	None
R/C	rs143556947	-0.652	1.0	N	0.711	0.486	None	gnomAD-4.0.0	2.23089E-05	None	None	None	None	N	None	1.73347E-04	1.667E-05	None	0	2.22846E-05	None	1.56323E-05	0	1.52573E-05	1.09803E-05	1.60051E-05
R/G	rs143556947	-1.266	1.0	N	0.691	0.422	0.673759014288	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
R/G	rs143556947	-1.266	1.0	N	0.691	0.422	0.673759014288	gnomAD-4.0.0	4.10532E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39684E-06	0	0
R/H	rs753958605	-1.4	1.0	N	0.737	0.378	0.384252928164	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	3.54E-05	0
R/H	rs753958605	-1.4	1.0	N	0.737	0.378	0.384252928164	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs753958605	-1.4	1.0	N	0.737	0.378	0.384252928164	gnomAD-4.0.0	6.19728E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.62862E-06	0	1.60123E-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	0.8839	likely_pathogenic	0.8893	pathogenic	-0.482	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
R/C	0.5929	likely_pathogenic	0.6663	pathogenic	-0.25	Destabilizing	1.0	D	0.711	prob.delet.	N	0.487542889	None	None	N
R/D	0.9407	likely_pathogenic	0.9447	pathogenic	-0.027	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
R/E	0.8139	likely_pathogenic	0.8187	pathogenic	0.094	Stabilizing	0.997	D	0.702	prob.neutral	None	None	None	None	N
R/F	0.8838	likely_pathogenic	0.8866	pathogenic	-0.312	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
R/G	0.7605	likely_pathogenic	0.7969	pathogenic	-0.803	Destabilizing	1.0	D	0.691	prob.neutral	N	0.452902463	None	None	N
R/H	0.328	likely_benign	0.362	ambiguous	-1.295	Destabilizing	1.0	D	0.737	prob.delet.	N	0.495117232	None	None	N
R/I	0.7142	likely_pathogenic	0.7102	pathogenic	0.375	Stabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
R/K	0.2755	likely_benign	0.2913	benign	-0.52	Destabilizing	0.979	D	0.538	neutral	None	None	None	None	N
R/L	0.6347	likely_pathogenic	0.6634	pathogenic	0.375	Stabilizing	1.0	D	0.691	prob.neutral	N	0.516935298	None	None	N
R/M	0.7557	likely_pathogenic	0.7645	pathogenic	0.07	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
R/N	0.8783	likely_pathogenic	0.8898	pathogenic	0.04	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
R/P	0.9468	likely_pathogenic	0.9512	pathogenic	0.111	Stabilizing	1.0	D	0.701	prob.neutral	N	0.489998424	None	None	N
R/Q	0.2877	likely_benign	0.3041	benign	-0.09	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
R/S	0.8977	likely_pathogenic	0.9089	pathogenic	-0.586	Destabilizing	1.0	D	0.709	prob.delet.	N	0.489516624	None	None	N
R/T	0.8008	likely_pathogenic	0.8021	pathogenic	-0.285	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
R/V	0.8069	likely_pathogenic	0.8152	pathogenic	0.111	Stabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
R/W	0.5857	likely_pathogenic	0.6119	pathogenic	-0.055	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
R/Y	0.7576	likely_pathogenic	0.7757	pathogenic	0.256	Stabilizing	0.999	D	0.715	prob.delet.	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.