TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30050	90373;90374;90375	chr2:178552752;178552751;178552750	chr2:179417479;179417478;179417477
N2AB	28409	85450;85451;85452	chr2:178552752;178552751;178552750	chr2:179417479;179417478;179417477
N2A	27482	82669;82670;82671	chr2:178552752;178552751;178552750	chr2:179417479;179417478;179417477
N2B	20985	63178;63179;63180	chr2:178552752;178552751;178552750	chr2:179417479;179417478;179417477
Novex-1	21110	63553;63554;63555	chr2:178552752;178552751;178552750	chr2:179417479;179417478;179417477
Novex-2	21177	63754;63755;63756	chr2:178552752;178552751;178552750	chr2:179417479;179417478;179417477
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-107
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1943
• 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
S/T	rs752534032	-0.49	None	N	0.193	0.108	0.0401082797425	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
S/T	rs752534032	-0.49	None	N	0.193	0.108	0.0401082797425	gnomAD-4.0.0	4.10501E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99433E-07	5.79656E-05	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
S/A	0.0763	likely_benign	0.0815	benign	-0.758	Destabilizing	None	N	0.174	neutral	None	None	None	None	N
S/C	0.0756	likely_benign	0.0679	benign	-0.56	Destabilizing	0.56	D	0.545	neutral	N	0.51902588	None	None	N
S/D	0.4143	ambiguous	0.3445	ambiguous	-1.262	Destabilizing	0.016	N	0.259	neutral	None	None	None	None	N
S/E	0.412	ambiguous	0.3781	ambiguous	-1.09	Destabilizing	0.016	N	0.283	neutral	None	None	None	None	N
S/F	0.1583	likely_benign	0.1555	benign	-0.622	Destabilizing	0.214	N	0.584	neutral	None	None	None	None	N
S/G	0.0846	likely_benign	0.0796	benign	-1.143	Destabilizing	0.012	N	0.263	neutral	N	0.486913462	None	None	N
S/H	0.1746	likely_benign	0.1446	benign	-1.551	Destabilizing	None	N	0.299	neutral	None	None	None	None	N
S/I	0.1427	likely_benign	0.1226	benign	0.211	Stabilizing	0.029	N	0.541	neutral	D	0.524778417	None	None	N
S/K	0.4324	ambiguous	0.3776	ambiguous	-0.295	Destabilizing	0.016	N	0.268	neutral	None	None	None	None	N
S/L	0.0897	likely_benign	0.094	benign	0.211	Stabilizing	0.016	N	0.385	neutral	None	None	None	None	N
S/M	0.1542	likely_benign	0.1476	benign	0.108	Stabilizing	0.356	N	0.547	neutral	None	None	None	None	N
S/N	0.0998	likely_benign	0.0838	benign	-0.892	Destabilizing	None	N	0.185	neutral	N	0.481198211	None	None	N
S/P	0.8802	likely_pathogenic	0.8493	pathogenic	-0.077	Destabilizing	0.136	N	0.472	neutral	None	None	None	None	N
S/Q	0.257	likely_benign	0.227	benign	-0.69	Destabilizing	None	N	0.175	neutral	None	None	None	None	N
S/R	0.343	ambiguous	0.3046	benign	-0.634	Destabilizing	0.029	N	0.401	neutral	N	0.479157983	None	None	N
S/T	0.0713	likely_benign	0.0705	benign	-0.587	Destabilizing	None	N	0.193	neutral	N	0.423688703	None	None	N
S/V	0.1529	likely_benign	0.1435	benign	-0.077	Destabilizing	0.016	N	0.375	neutral	None	None	None	None	N
S/W	0.2766	likely_benign	0.2473	benign	-0.871	Destabilizing	0.864	D	0.596	neutral	None	None	None	None	N
S/Y	0.1399	likely_benign	0.1273	benign	-0.421	Destabilizing	0.038	N	0.56	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.