TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27712	83359;83360;83361	chr2:178562998;178562997;178562996	chr2:179427725;179427724;179427723
N2AB	26071	78436;78437;78438	chr2:178562998;178562997;178562996	chr2:179427725;179427724;179427723
N2A	25144	75655;75656;75657	chr2:178562998;178562997;178562996	chr2:179427725;179427724;179427723
N2B	18647	56164;56165;56166	chr2:178562998;178562997;178562996	chr2:179427725;179427724;179427723
Novex-1	18772	56539;56540;56541	chr2:178562998;178562997;178562996	chr2:179427725;179427724;179427723
Novex-2	18839	56740;56741;56742	chr2:178562998;178562997;178562996	chr2:179427725;179427724;179427723
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-141
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.6759
• Predicted PPI site: I

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
A/T	None	None	0.892	N	0.445	0.2	0.28492961333	gnomAD-4.0.0	1.59155E-06	None	None	None	None	I	None	0	0	None	0	2.77454E-05	None	0	0	0	0	0
A/V	None	None	0.025	N	0.305	0.085	0.227260227426	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
A/C	0.5098	ambiguous	0.5189	ambiguous	-0.699	Destabilizing	0.999	D	0.481	neutral	None	None	None	None	I
A/D	0.2726	likely_benign	0.2599	benign	-0.821	Destabilizing	0.95	D	0.543	neutral	None	None	None	None	I
A/E	0.2367	likely_benign	0.219	benign	-0.978	Destabilizing	0.204	N	0.353	neutral	N	0.375379389	None	None	I
A/F	0.4112	ambiguous	0.409	ambiguous	-1.069	Destabilizing	0.975	D	0.618	neutral	None	None	None	None	I
A/G	0.1227	likely_benign	0.1219	benign	-0.553	Destabilizing	0.944	D	0.443	neutral	N	0.413857632	None	None	I
A/H	0.5255	ambiguous	0.5265	ambiguous	-0.636	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	I
A/I	0.2541	likely_benign	0.2494	benign	-0.472	Destabilizing	0.845	D	0.498	neutral	None	None	None	None	I
A/K	0.4948	ambiguous	0.4658	ambiguous	-0.835	Destabilizing	0.975	D	0.456	neutral	None	None	None	None	I
A/L	0.188	likely_benign	0.1922	benign	-0.472	Destabilizing	0.845	D	0.491	neutral	None	None	None	None	I
A/M	0.2108	likely_benign	0.2098	benign	-0.36	Destabilizing	0.997	D	0.51	neutral	None	None	None	None	I
A/N	0.2015	likely_benign	0.1997	benign	-0.408	Destabilizing	0.987	D	0.604	neutral	None	None	None	None	I
A/P	0.3212	likely_benign	0.338	benign	-0.44	Destabilizing	0.994	D	0.509	neutral	N	0.442777817	None	None	I
A/Q	0.3223	likely_benign	0.3125	benign	-0.748	Destabilizing	0.975	D	0.511	neutral	None	None	None	None	I
A/R	0.5104	ambiguous	0.4825	ambiguous	-0.305	Destabilizing	0.975	D	0.51	neutral	None	None	None	None	I
A/S	0.0912	likely_benign	0.0914	benign	-0.584	Destabilizing	0.892	D	0.461	neutral	N	0.453013453	None	None	I
A/T	0.093	likely_benign	0.0913	benign	-0.675	Destabilizing	0.892	D	0.445	neutral	N	0.507309298	None	None	I
A/V	0.1242	likely_benign	0.1231	benign	-0.44	Destabilizing	0.025	N	0.305	neutral	N	0.45495768	None	None	I
A/W	0.7886	likely_pathogenic	0.7806	pathogenic	-1.201	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	I
A/Y	0.519	ambiguous	0.5067	ambiguous	-0.869	Destabilizing	0.987	D	0.613	neutral	None	None	None	None	I

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.