TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34332	103219;103220;103221	chr2:178533621;178533620;178533619	chr2:179398348;179398347;179398346
N2AB	32691	98296;98297;98298	chr2:178533621;178533620;178533619	chr2:179398348;179398347;179398346
N2A	31764	95515;95516;95517	chr2:178533621;178533620;178533619	chr2:179398348;179398347;179398346
N2B	25267	76024;76025;76026	chr2:178533621;178533620;178533619	chr2:179398348;179398347;179398346
Novex-1	25392	76399;76400;76401	chr2:178533621;178533620;178533619	chr2:179398348;179398347;179398346
Novex-2	25459	76600;76601;76602	chr2:178533621;178533620;178533619	chr2:179398348;179398347;179398346
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-161
• Domain position: 75
• Structural Position: 155
• Q(SASA): 0.1469
• 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
T/A	rs1450806366	-1.379	None	N	0.291	0.123	0.0482279557977	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	9.2081E-04
T/A	rs1450806366	-1.379	None	N	0.291	0.123	0.0482279557977	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	0	0	1.43678E-03
T/A	rs1450806366	-1.379	None	N	0.291	0.123	0.0482279557977	gnomAD-4.0.0	5.07448E-06	None	None	None	None	N	None	0	6.14704E-05	None	0	0	None	0	0	0	0	1.36119E-04

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
T/A	0.1059	likely_benign	0.1496	benign	-1.37	Destabilizing	None	N	0.291	neutral	N	0.485290869	None	None	N
T/C	0.508	ambiguous	0.592	pathogenic	-0.661	Destabilizing	0.883	D	0.595	neutral	None	None	None	None	N
T/D	0.6477	likely_pathogenic	0.7987	pathogenic	-1.446	Destabilizing	0.22	N	0.555	neutral	None	None	None	None	N
T/E	0.4363	ambiguous	0.5538	ambiguous	-1.172	Destabilizing	0.124	N	0.547	neutral	None	None	None	None	N
T/F	0.3616	ambiguous	0.4924	ambiguous	-0.952	Destabilizing	0.497	N	0.583	neutral	None	None	None	None	N
T/G	0.4245	ambiguous	0.591	pathogenic	-1.808	Destabilizing	None	N	0.48	neutral	None	None	None	None	N
T/H	0.4047	ambiguous	0.4931	ambiguous	-1.604	Destabilizing	0.667	D	0.604	neutral	None	None	None	None	N
T/I	0.2268	likely_benign	0.3069	benign	-0.18	Destabilizing	0.096	N	0.564	neutral	N	0.482615923	None	None	N
T/K	0.3663	ambiguous	0.5164	ambiguous	0.057	Stabilizing	0.124	N	0.541	neutral	None	None	None	None	N
T/L	0.1434	likely_benign	0.2269	benign	-0.18	Destabilizing	0.055	N	0.514	neutral	None	None	None	None	N
T/M	0.0927	likely_benign	0.1372	benign	-0.401	Destabilizing	0.025	N	0.486	neutral	None	None	None	None	N
T/N	0.2636	likely_benign	0.3833	ambiguous	-0.797	Destabilizing	0.096	N	0.505	neutral	N	0.469315101	None	None	N
T/P	0.8929	likely_pathogenic	0.9632	pathogenic	-0.55	Destabilizing	0.301	N	0.599	neutral	N	0.48134297	None	None	N
T/Q	0.3533	ambiguous	0.4442	ambiguous	-0.467	Destabilizing	0.497	N	0.593	neutral	None	None	None	None	N
T/R	0.2778	likely_benign	0.4212	ambiguous	-0.338	Destabilizing	0.001	N	0.48	neutral	None	None	None	None	N
T/S	0.1479	likely_benign	0.1877	benign	-1.101	Destabilizing	None	N	0.249	neutral	N	0.424279696	None	None	N
T/V	0.174	likely_benign	0.2156	benign	-0.55	Destabilizing	0.055	N	0.446	neutral	None	None	None	None	N
T/W	0.7041	likely_pathogenic	0.8227	pathogenic	-1.05	Destabilizing	0.958	D	0.644	neutral	None	None	None	None	N
T/Y	0.4277	ambiguous	0.5685	pathogenic	-0.657	Destabilizing	0.667	D	0.581	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.