TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4982	15169;15170;15171	chr2:178734980;178734979;178734978	chr2:179599707;179599706;179599705
N2AB	4665	14218;14219;14220	chr2:178734980;178734979;178734978	chr2:179599707;179599706;179599705
N2A	3738	11437;11438;11439	chr2:178734980;178734979;178734978	chr2:179599707;179599706;179599705
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-33
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3576
• 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	rs775173260	0.122	None	N	0.165	0.049	0.0297737177859	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/T	rs775173260	0.122	None	N	0.165	0.049	0.0297737177859	gnomAD-4.0.0	6.5697E-06	None	None	None	None	N	None	2.41208E-05	0	None	0	0	None	0	0	0	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
S/A	0.0611	likely_benign	0.061	benign	-0.49	Destabilizing	None	N	0.134	neutral	N	0.450492574	None	None	N
S/C	0.1111	likely_benign	0.1109	benign	-0.358	Destabilizing	None	N	0.214	neutral	N	0.49041911	None	None	N
S/D	0.6399	likely_pathogenic	0.6558	pathogenic	0.489	Stabilizing	0.072	N	0.287	neutral	None	None	None	None	N
S/E	0.6476	likely_pathogenic	0.6576	pathogenic	0.481	Stabilizing	0.072	N	0.258	neutral	None	None	None	None	N
S/F	0.1585	likely_benign	0.1627	benign	-0.761	Destabilizing	0.295	N	0.435	neutral	N	0.448318746	None	None	N
S/G	0.1205	likely_benign	0.1255	benign	-0.713	Destabilizing	0.016	N	0.281	neutral	None	None	None	None	N
S/H	0.4053	ambiguous	0.4166	ambiguous	-1.041	Destabilizing	0.864	D	0.347	neutral	None	None	None	None	N
S/I	0.1285	likely_benign	0.1319	benign	-0.014	Destabilizing	0.038	N	0.355	neutral	None	None	None	None	N
S/K	0.7617	likely_pathogenic	0.758	pathogenic	-0.301	Destabilizing	0.072	N	0.257	neutral	None	None	None	None	N
S/L	0.0821	likely_benign	0.0827	benign	-0.014	Destabilizing	0.016	N	0.335	neutral	None	None	None	None	N
S/M	0.1625	likely_benign	0.1739	benign	-0.022	Destabilizing	0.356	N	0.338	neutral	None	None	None	None	N
S/N	0.2034	likely_benign	0.2211	benign	-0.262	Destabilizing	0.136	N	0.363	neutral	None	None	None	None	N
S/P	0.856	likely_pathogenic	0.8191	pathogenic	-0.139	Destabilizing	0.055	N	0.385	neutral	N	0.452207144	None	None	N
S/Q	0.5254	ambiguous	0.5326	ambiguous	-0.341	Destabilizing	0.356	N	0.372	neutral	None	None	None	None	N
S/R	0.6609	likely_pathogenic	0.6598	pathogenic	-0.237	Destabilizing	0.214	N	0.396	neutral	None	None	None	None	N
S/T	0.0706	likely_benign	0.0747	benign	-0.334	Destabilizing	None	N	0.165	neutral	N	0.43071254	None	None	N
S/V	0.108	likely_benign	0.1122	benign	-0.139	Destabilizing	0.001	N	0.358	neutral	None	None	None	None	N
S/W	0.4075	ambiguous	0.3954	ambiguous	-0.767	Destabilizing	0.864	D	0.497	neutral	None	None	None	None	N
S/Y	0.1828	likely_benign	0.1819	benign	-0.458	Destabilizing	0.295	N	0.429	neutral	N	0.450707291	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.