TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29391	88396;88397;88398	chr2:178556983;178556982;178556981	chr2:179421710;179421709;179421708
N2AB	27750	83473;83474;83475	chr2:178556983;178556982;178556981	chr2:179421710;179421709;179421708
N2A	26823	80692;80693;80694	chr2:178556983;178556982;178556981	chr2:179421710;179421709;179421708
N2B	20326	61201;61202;61203	chr2:178556983;178556982;178556981	chr2:179421710;179421709;179421708
Novex-1	20451	61576;61577;61578	chr2:178556983;178556982;178556981	chr2:179421710;179421709;179421708
Novex-2	20518	61777;61778;61779	chr2:178556983;178556982;178556981	chr2:179421710;179421709;179421708
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-102
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.4905
• 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
T/S	rs771850921	-1.009	0.002	N	0.159	0.084	0.0482279557977	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
T/S	rs771850921	-1.009	0.002	N	0.159	0.084	0.0482279557977	gnomAD-4.0.0	1.36844E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79889E-06	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
T/A	0.0739	likely_benign	0.0718	benign	-0.623	Destabilizing	0.012	N	0.293	neutral	N	0.486755959	None	None	N
T/C	0.4175	ambiguous	0.3855	ambiguous	-0.429	Destabilizing	0.864	D	0.489	neutral	None	None	None	None	N
T/D	0.4718	ambiguous	0.3772	ambiguous	0.325	Stabilizing	None	N	0.251	neutral	None	None	None	None	N
T/E	0.3371	likely_benign	0.2602	benign	0.277	Stabilizing	0.038	N	0.447	neutral	None	None	None	None	N
T/F	0.2588	likely_benign	0.1924	benign	-0.998	Destabilizing	0.214	N	0.573	neutral	None	None	None	None	N
T/G	0.2043	likely_benign	0.1889	benign	-0.791	Destabilizing	0.072	N	0.457	neutral	None	None	None	None	N
T/H	0.2805	likely_benign	0.2516	benign	-0.995	Destabilizing	0.864	D	0.521	neutral	None	None	None	None	N
T/I	0.1058	likely_benign	0.0713	benign	-0.291	Destabilizing	None	N	0.213	neutral	N	0.454184968	None	None	N
T/K	0.2083	likely_benign	0.1756	benign	-0.416	Destabilizing	0.072	N	0.47	neutral	None	None	None	None	N
T/L	0.0649	likely_benign	0.0555	benign	-0.291	Destabilizing	0.002	N	0.294	neutral	None	None	None	None	N
T/M	0.0668	likely_benign	0.0617	benign	-0.161	Destabilizing	0.007	N	0.28	neutral	None	None	None	None	N
T/N	0.1134	likely_benign	0.1041	benign	-0.295	Destabilizing	0.055	N	0.45	neutral	N	0.479235341	None	None	N
T/P	0.0831	likely_benign	0.0803	benign	-0.372	Destabilizing	0.56	D	0.577	neutral	N	0.435887209	None	None	N
T/Q	0.2117	likely_benign	0.1983	benign	-0.473	Destabilizing	0.356	N	0.571	neutral	None	None	None	None	N
T/R	0.1863	likely_benign	0.1526	benign	-0.148	Destabilizing	0.356	N	0.582	neutral	None	None	None	None	N
T/S	0.1003	likely_benign	0.0999	benign	-0.576	Destabilizing	0.002	N	0.159	neutral	N	0.424150063	None	None	N
T/V	0.1051	likely_benign	0.0834	benign	-0.372	Destabilizing	0.006	N	0.229	neutral	None	None	None	None	N
T/W	0.6242	likely_pathogenic	0.5427	ambiguous	-0.953	Destabilizing	0.864	D	0.563	neutral	None	None	None	None	N
T/Y	0.34	ambiguous	0.2864	benign	-0.691	Destabilizing	0.356	N	0.557	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.