TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23420	70483;70484;70485	chr2:178575874;178575873;178575872	chr2:179440601;179440600;179440599
N2AB	21779	65560;65561;65562	chr2:178575874;178575873;178575872	chr2:179440601;179440600;179440599
N2A	20852	62779;62780;62781	chr2:178575874;178575873;178575872	chr2:179440601;179440600;179440599
N2B	14355	43288;43289;43290	chr2:178575874;178575873;178575872	chr2:179440601;179440600;179440599
Novex-1	14480	43663;43664;43665	chr2:178575874;178575873;178575872	chr2:179440601;179440600;179440599
Novex-2	14547	43864;43865;43866	chr2:178575874;178575873;178575872	chr2:179440601;179440600;179440599
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Ig-129
• Domain position: 76
• Structural Position: 162
• Q(SASA): 0.6706
• 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
P/L	rs776633672	-0.018	0.029	N	0.375	0.143	0.481690325388	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	0	2.02793E-04	None	0	0	None	0	None	0	8.88E-06	0
P/L	rs776633672	-0.018	0.029	N	0.375	0.143	0.481690325388	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96773E-04	0	0	0	None	0	0	0	0	0
P/L	rs776633672	-0.018	0.029	N	0.375	0.143	0.481690325388	gnomAD-4.0.0	1.17766E-05	None	None	None	None	N	None	0	1.83437E-04	None	0	2.23055E-05	None	0	0	5.93413E-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
P/A	0.0512	likely_benign	0.0615	benign	-0.297	Destabilizing	None	N	0.135	neutral	N	0.423870422	None	None	N
P/C	0.3655	ambiguous	0.478	ambiguous	-0.65	Destabilizing	0.356	N	0.285	neutral	None	None	None	None	N
P/D	0.2772	likely_benign	0.359	ambiguous	-0.321	Destabilizing	0.072	N	0.32	neutral	None	None	None	None	N
P/E	0.1848	likely_benign	0.2263	benign	-0.448	Destabilizing	0.072	N	0.32	neutral	None	None	None	None	N
P/F	0.3708	ambiguous	0.4907	ambiguous	-0.714	Destabilizing	0.214	N	0.308	neutral	None	None	None	None	N
P/G	0.1906	likely_benign	0.2459	benign	-0.365	Destabilizing	0.016	N	0.342	neutral	None	None	None	None	N
P/H	0.1575	likely_benign	0.1888	benign	-0.029	Destabilizing	0.628	D	0.297	neutral	None	None	None	None	N
P/I	0.1603	likely_benign	0.2055	benign	-0.27	Destabilizing	0.006	N	0.36	neutral	None	None	None	None	N
P/K	0.1678	likely_benign	0.2075	benign	-0.326	Destabilizing	0.072	N	0.331	neutral	None	None	None	None	N
P/L	0.0906	likely_benign	0.0896	benign	-0.27	Destabilizing	0.029	N	0.375	neutral	N	0.452846535	None	None	N
P/M	0.1823	likely_benign	0.229	benign	-0.417	Destabilizing	0.214	N	0.3	neutral	None	None	None	None	N
P/N	0.1876	likely_benign	0.2375	benign	-0.078	Destabilizing	0.356	N	0.332	neutral	None	None	None	None	N
P/Q	0.1286	likely_benign	0.1517	benign	-0.316	Destabilizing	0.515	D	0.287	neutral	N	0.48024378	None	None	N
P/R	0.1447	likely_benign	0.1736	benign	0.14	Stabilizing	0.344	N	0.338	neutral	N	0.458791072	None	None	N
P/S	0.0953	likely_benign	0.1133	benign	-0.375	Destabilizing	0.012	N	0.337	neutral	N	0.384021168	None	None	N
P/T	0.0701	likely_benign	0.082	benign	-0.41	Destabilizing	0.012	N	0.349	neutral	N	0.45438533	None	None	N
P/V	0.1089	likely_benign	0.1346	benign	-0.249	Destabilizing	None	N	0.134	neutral	None	None	None	None	N
P/W	0.5767	likely_pathogenic	0.7006	pathogenic	-0.788	Destabilizing	0.864	D	0.304	neutral	None	None	None	None	N
P/Y	0.3372	likely_benign	0.4454	ambiguous	-0.489	Destabilizing	0.356	N	0.307	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.