TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15997	48214;48215;48216	chr2:178616900;178616899;178616898	chr2:179481627;179481626;179481625
N2AB	14356	43291;43292;43293	chr2:178616900;178616899;178616898	chr2:179481627;179481626;179481625
N2A	13429	40510;40511;40512	chr2:178616900;178616899;178616898	chr2:179481627;179481626;179481625
N2B	6932	21019;21020;21021	chr2:178616900;178616899;178616898	chr2:179481627;179481626;179481625
Novex-1	7057	21394;21395;21396	chr2:178616900;178616899;178616898	chr2:179481627;179481626;179481625
Novex-2	7124	21595;21596;21597	chr2:178616900;178616899;178616898	chr2:179481627;179481626;179481625
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-109
• Domain position: 30
• Structural Position: 49
• Q(SASA): 0.1745
• 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
C/R	rs2057436649	None	0.007	N	0.509	0.082	0.232513804876	gnomAD-4.0.0	2.05383E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6996E-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
C/A	0.2229	likely_benign	0.2309	benign	-1.645	Destabilizing	None	N	0.221	neutral	None	None	None	None	N
C/D	0.4147	ambiguous	0.4332	ambiguous	-0.445	Destabilizing	0.002	N	0.461	neutral	None	None	None	None	N
C/E	0.3693	ambiguous	0.3752	ambiguous	-0.274	Destabilizing	0.002	N	0.465	neutral	None	None	None	None	N
C/F	0.1107	likely_benign	0.1105	benign	-1.081	Destabilizing	0.013	N	0.493	neutral	N	0.346499013	None	None	N
C/G	0.1275	likely_benign	0.1409	benign	-1.991	Destabilizing	0.001	N	0.484	neutral	N	0.384675865	None	None	N
C/H	0.1517	likely_benign	0.1534	benign	-2.149	Highly Destabilizing	0.132	N	0.583	neutral	None	None	None	None	N
C/I	0.2237	likely_benign	0.2376	benign	-0.734	Destabilizing	None	N	0.257	neutral	None	None	None	None	N
C/K	0.3701	ambiguous	0.3592	ambiguous	-0.641	Destabilizing	0.002	N	0.467	neutral	None	None	None	None	N
C/L	0.1732	likely_benign	0.1983	benign	-0.734	Destabilizing	None	N	0.289	neutral	None	None	None	None	N
C/M	0.2801	likely_benign	0.2793	benign	0.129	Stabilizing	0.041	N	0.505	neutral	None	None	None	None	N
C/N	0.1545	likely_benign	0.1721	benign	-0.945	Destabilizing	0.002	N	0.457	neutral	None	None	None	None	N
C/P	0.9775	likely_pathogenic	0.9797	pathogenic	-1.012	Destabilizing	0.009	N	0.501	neutral	None	None	None	None	N
C/Q	0.2745	likely_benign	0.2538	benign	-0.655	Destabilizing	0.009	N	0.52	neutral	None	None	None	None	N
C/R	0.1774	likely_benign	0.1755	benign	-0.882	Destabilizing	0.007	N	0.509	neutral	N	0.38365418	None	None	N
C/S	0.1035	likely_benign	0.1082	benign	-1.415	Destabilizing	None	N	0.249	neutral	N	0.284870748	None	None	N
C/T	0.1482	likely_benign	0.1408	benign	-1.038	Destabilizing	None	N	0.25	neutral	None	None	None	None	N
C/V	0.2243	likely_benign	0.227	benign	-1.012	Destabilizing	None	N	0.247	neutral	None	None	None	None	N
C/W	0.2961	likely_benign	0.2939	benign	-1.218	Destabilizing	0.258	N	0.525	neutral	N	0.396762554	None	None	N
C/Y	0.1323	likely_benign	0.1269	benign	-1.099	Destabilizing	0.013	N	0.509	neutral	N	0.310833203	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.