TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16132	48619;48620;48621	chr2:178615707;178615706;178615705	chr2:179480434;179480433;179480432
N2AB	14491	43696;43697;43698	chr2:178615707;178615706;178615705	chr2:179480434;179480433;179480432
N2A	13564	40915;40916;40917	chr2:178615707;178615706;178615705	chr2:179480434;179480433;179480432
N2B	7067	21424;21425;21426	chr2:178615707;178615706;178615705	chr2:179480434;179480433;179480432
Novex-1	7192	21799;21800;21801	chr2:178615707;178615706;178615705	chr2:179480434;179480433;179480432
Novex-2	7259	22000;22001;22002	chr2:178615707;178615706;178615705	chr2:179480434;179480433;179480432
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: Fn3-4
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.3759
• 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	rs2303830	-1.403	None	N	0.355	0.111	None	gnomAD-2.1.1	1.60964E-04	None	None	None	None	N	None	8.28E-05	2.83E-05	None	0	1.75547E-03	None	0	None	1.19923E-04	7.83E-06	5.62905E-04
R/C	rs2303830	-1.403	None	N	0.355	0.111	None	gnomAD-3.1.2	2.43674E-04	None	None	None	None	N	None	7.25E-05	0	0	0	6.04053E-03	None	9.43E-05	0	2.95E-05	0	0
R/C	rs2303830	-1.403	None	N	0.355	0.111	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	3E-03	0	None	None	None	0	None
R/C	rs2303830	-1.403	None	N	0.355	0.111	None	gnomAD-4.0.0	3.15067E-04	None	None	None	None	N	None	5.34174E-05	0	None	0	1.08229E-02	None	9.37559E-05	0	5.0894E-06	0	1.28197E-04
R/H	rs397517593	-1.778	0.877	N	0.517	0.217	0.252162846088	gnomAD-2.1.1	5.37E-05	None	None	None	None	N	None	8.28E-05	1.41667E-04	None	0	5.16E-05	None	9.81E-05	None	0	3.13E-05	0
R/H	rs397517593	-1.778	0.877	N	0.517	0.217	0.252162846088	gnomAD-3.1.2	1.98E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs397517593	-1.778	0.877	N	0.517	0.217	0.252162846088	gnomAD-4.0.0	5.21002E-05	None	None	None	None	N	None	2.40674E-04	1.00177E-04	None	0	2.23484E-05	None	0	8.24266E-04	2.20538E-05	2.30739E-04	1.12208E-04

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	0.3799	ambiguous	0.4839	ambiguous	-1.589	Destabilizing	0.007	N	0.213	neutral	None	None	None	None	N
R/C	0.0977	likely_benign	0.1305	benign	-1.775	Destabilizing	None	N	0.355	neutral	N	0.410106538	None	None	N
R/D	0.7872	likely_pathogenic	0.8579	pathogenic	-0.825	Destabilizing	0.325	N	0.557	neutral	None	None	None	None	N
R/E	0.3608	ambiguous	0.417	ambiguous	-0.668	Destabilizing	0.325	N	0.43	neutral	None	None	None	None	N
R/F	0.4243	ambiguous	0.5277	ambiguous	-1.302	Destabilizing	0.356	N	0.586	neutral	None	None	None	None	N
R/G	0.3423	ambiguous	0.4362	ambiguous	-1.902	Destabilizing	0.13	N	0.502	neutral	N	0.481328932	None	None	N
R/H	0.1135	likely_benign	0.1436	benign	-1.824	Destabilizing	0.877	D	0.517	neutral	N	0.433604177	None	None	N
R/I	0.1843	likely_benign	0.2201	benign	-0.714	Destabilizing	None	N	0.352	neutral	None	None	None	None	N
R/K	0.1006	likely_benign	0.1176	benign	-1.511	Destabilizing	0.061	N	0.377	neutral	None	None	None	None	N
R/L	0.215	likely_benign	0.2804	benign	-0.714	Destabilizing	0.013	N	0.262	neutral	N	0.459103579	None	None	N
R/M	0.2214	likely_benign	0.2776	benign	-1.048	Destabilizing	0.356	N	0.531	neutral	None	None	None	None	N
R/N	0.596	likely_pathogenic	0.705	pathogenic	-1.17	Destabilizing	0.136	N	0.471	neutral	None	None	None	None	N
R/P	0.9528	likely_pathogenic	0.9636	pathogenic	-0.99	Destabilizing	0.764	D	0.595	neutral	N	0.469911025	None	None	N
R/Q	0.0885	likely_benign	0.1071	benign	-1.265	Destabilizing	0.325	N	0.506	neutral	None	None	None	None	N
R/S	0.4295	ambiguous	0.5393	ambiguous	-2.039	Highly Destabilizing	0.058	N	0.409	neutral	N	0.46577769	None	None	N
R/T	0.1957	likely_benign	0.2531	benign	-1.689	Destabilizing	0.031	N	0.408	neutral	None	None	None	None	N
R/V	0.211	likely_benign	0.2571	benign	-0.99	Destabilizing	0.007	N	0.285	neutral	None	None	None	None	N
R/W	0.1765	likely_benign	0.2237	benign	-0.863	Destabilizing	0.864	D	0.519	neutral	None	None	None	None	N
R/Y	0.2936	likely_benign	0.3856	ambiguous	-0.589	Destabilizing	0.628	D	0.581	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.