TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26619	80080;80081;80082	chr2:178566277;178566276;178566275	chr2:179431004;179431003;179431002
N2AB	24978	75157;75158;75159	chr2:178566277;178566276;178566275	chr2:179431004;179431003;179431002
N2A	24051	72376;72377;72378	chr2:178566277;178566276;178566275	chr2:179431004;179431003;179431002
N2B	17554	52885;52886;52887	chr2:178566277;178566276;178566275	chr2:179431004;179431003;179431002
Novex-1	17679	53260;53261;53262	chr2:178566277;178566276;178566275	chr2:179431004;179431003;179431002
Novex-2	17746	53461;53462;53463	chr2:178566277;178566276;178566275	chr2:179431004;179431003;179431002
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: Ig-138
• Domain position: 26
• Structural Position: 41
• Q(SASA): 0.4623
• 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	rs757229467	-0.088	0.047	N	0.537	0.338	0.499727662827	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	0	5.8E-05	None	0	1.11408E-04	None	3.27E-05	None	0	3.55E-05	0
R/C	rs757229467	-0.088	0.047	N	0.537	0.338	0.499727662827	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	4.77555E-04
R/C	rs757229467	-0.088	0.047	N	0.537	0.338	0.499727662827	gnomAD-4.0.0	1.23958E-05	None	None	None	None	N	None	0	5.00417E-05	None	0	4.4603E-05	None	0	0	9.32439E-06	1.09801E-05	4.80384E-05
R/H	rs530507211	-0.82	0.047	D	0.291	0.235	0.202086224978	gnomAD-2.1.1	3.25466E-04	None	None	None	None	N	None	0	2.11496E-03	None	0	5.57E-05	None	1.3071E-04	None	0	2.66E-05	0
R/H	rs530507211	-0.82	0.047	D	0.291	0.235	0.202086224978	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	0	2.62398E-04	0	0	0	None	0	0	2.94E-05	0	0
R/H	rs530507211	-0.82	0.047	D	0.291	0.235	0.202086224978	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
R/H	rs530507211	-0.82	0.047	D	0.291	0.235	0.202086224978	gnomAD-4.0.0	6.631E-05	None	None	None	None	N	None	1.33323E-05	1.31715E-03	None	6.75721E-05	2.23025E-05	None	0	0	9.32448E-06	1.20778E-04	3.20164E-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	0.9719	likely_pathogenic	0.968	pathogenic	0.071	Stabilizing	0.25	N	0.498	neutral	None	None	None	None	N
R/C	0.4947	ambiguous	0.4658	ambiguous	-0.075	Destabilizing	0.047	N	0.537	neutral	N	0.515179797	None	None	N
R/D	0.9918	likely_pathogenic	0.9921	pathogenic	-0.222	Destabilizing	0.92	D	0.556	neutral	None	None	None	None	N
R/E	0.9411	likely_pathogenic	0.9427	pathogenic	-0.175	Destabilizing	0.617	D	0.436	neutral	None	None	None	None	N
R/F	0.8806	likely_pathogenic	0.8645	pathogenic	-0.198	Destabilizing	0.85	D	0.552	neutral	None	None	None	None	N
R/G	0.9567	likely_pathogenic	0.9523	pathogenic	-0.091	Destabilizing	0.756	D	0.583	neutral	N	0.521674257	None	None	N
R/H	0.2748	likely_benign	0.2546	benign	-0.612	Destabilizing	0.047	N	0.291	neutral	D	0.528517729	None	None	N
R/I	0.7327	likely_pathogenic	0.6885	pathogenic	0.454	Stabilizing	0.447	N	0.556	neutral	None	None	None	None	N
R/K	0.278	likely_benign	0.2594	benign	-0.038	Destabilizing	0.766	D	0.413	neutral	None	None	None	None	N
R/L	0.8042	likely_pathogenic	0.7677	pathogenic	0.454	Stabilizing	0.608	D	0.548	neutral	N	0.503063023	None	None	N
R/M	0.8434	likely_pathogenic	0.816	pathogenic	0.037	Stabilizing	0.92	D	0.494	neutral	None	None	None	None	N
R/N	0.9579	likely_pathogenic	0.96	pathogenic	0.154	Stabilizing	0.617	D	0.45	neutral	None	None	None	None	N
R/P	0.9973	likely_pathogenic	0.9972	pathogenic	0.345	Stabilizing	0.985	D	0.572	neutral	D	0.533284052	None	None	N
R/Q	0.3695	ambiguous	0.355	ambiguous	0.077	Stabilizing	0.92	D	0.48	neutral	None	None	None	None	N
R/S	0.9662	likely_pathogenic	0.9635	pathogenic	-0.073	Destabilizing	0.756	D	0.529	neutral	D	0.522647762	None	None	N
R/T	0.9299	likely_pathogenic	0.9183	pathogenic	0.087	Stabilizing	0.617	D	0.526	neutral	None	None	None	None	N
R/V	0.8542	likely_pathogenic	0.8244	pathogenic	0.345	Stabilizing	0.005	N	0.44	neutral	None	None	None	None	N
R/W	0.4765	ambiguous	0.4507	ambiguous	-0.336	Destabilizing	0.992	D	0.599	neutral	None	None	None	None	N
R/Y	0.7012	likely_pathogenic	0.696	pathogenic	0.07	Stabilizing	0.85	D	0.567	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.