TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4664	14215;14216;14217	chr2:178739243;178739242;178739241	chr2:179603970;179603969;179603968
N2AB	4347	13264;13265;13266	chr2:178739243;178739242;178739241	chr2:179603970;179603969;179603968
N2A	None	None	chr2:None	chr2:None
N2B	4301	13126;13127;13128	chr2:178739243;178739242;178739241	chr2:179603970;179603969;179603968
Novex-1	4426	13501;13502;13503	chr2:178739243;178739242;178739241	chr2:179603970;179603969;179603968
Novex-2	4493	13702;13703;13704	chr2:178739243;178739242;178739241	chr2:179603970;179603969;179603968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-29
• Domain position: 59
• Structural Position: 141
• Q(SASA): 0.3541
• 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
D/N	rs767084399	-0.919	None	N	0.045	0.126	None	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.19E-06	0
D/N	rs767084399	-0.919	None	N	0.045	0.126	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
D/N	rs767084399	-0.919	None	N	0.045	0.126	None	gnomAD-4.0.0	6.27357E-06	None	None	None	None	N	None	0	1.68982E-05	None	0	6.75007E-05	None	0	0	1.71365E-06	1.13173E-05	4.8752E-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
D/A	0.149	likely_benign	0.1535	benign	-0.475	Destabilizing	0.005	N	0.299	neutral	N	0.466986724	None	None	N
D/C	0.4147	ambiguous	0.4486	ambiguous	-0.158	Destabilizing	0.864	D	0.445	neutral	None	None	None	None	N
D/E	0.1397	likely_benign	0.1371	benign	-0.576	Destabilizing	None	N	0.079	neutral	N	0.444768845	None	None	N
D/F	0.489	ambiguous	0.4917	ambiguous	-0.186	Destabilizing	0.214	N	0.537	neutral	None	None	None	None	N
D/G	0.1073	likely_benign	0.1111	benign	-0.789	Destabilizing	0.005	N	0.329	neutral	N	0.505075478	None	None	N
D/H	0.1371	likely_benign	0.1458	benign	-0.5	Destabilizing	None	N	0.218	neutral	N	0.456891461	None	None	N
D/I	0.3599	ambiguous	0.3734	ambiguous	0.342	Stabilizing	0.072	N	0.553	neutral	None	None	None	None	N
D/K	0.2098	likely_benign	0.2149	benign	-0.236	Destabilizing	0.016	N	0.379	neutral	None	None	None	None	N
D/L	0.2883	likely_benign	0.2972	benign	0.342	Stabilizing	0.031	N	0.446	neutral	None	None	None	None	N
D/M	0.5178	ambiguous	0.5311	ambiguous	0.702	Stabilizing	0.628	D	0.467	neutral	None	None	None	None	N
D/N	0.0715	likely_benign	0.0749	benign	-0.593	Destabilizing	None	N	0.045	neutral	N	0.422623511	None	None	N
D/P	0.4339	ambiguous	0.4664	ambiguous	0.095	Stabilizing	0.136	N	0.435	neutral	None	None	None	None	N
D/Q	0.2002	likely_benign	0.2114	benign	-0.495	Destabilizing	0.038	N	0.253	neutral	None	None	None	None	N
D/R	0.2093	likely_benign	0.2236	benign	-0.104	Destabilizing	None	N	0.225	neutral	None	None	None	None	N
D/S	0.087	likely_benign	0.0934	benign	-0.814	Destabilizing	None	N	0.045	neutral	None	None	None	None	N
D/T	0.1924	likely_benign	0.1997	benign	-0.563	Destabilizing	None	N	0.072	neutral	None	None	None	None	N
D/V	0.2352	likely_benign	0.2427	benign	0.095	Stabilizing	0.029	N	0.517	neutral	N	0.497979613	None	None	N
D/W	0.7162	likely_pathogenic	0.7347	pathogenic	-0.024	Destabilizing	0.864	D	0.463	neutral	None	None	None	None	N
D/Y	0.16	likely_benign	0.1668	benign	0.046	Stabilizing	0.208	N	0.551	neutral	N	0.513380518	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.