TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24282	73069;73070;73071	chr2:178573288;178573287;178573286	chr2:179438015;179438014;179438013
N2AB	22641	68146;68147;68148	chr2:178573288;178573287;178573286	chr2:179438015;179438014;179438013
N2A	21714	65365;65366;65367	chr2:178573288;178573287;178573286	chr2:179438015;179438014;179438013
N2B	15217	45874;45875;45876	chr2:178573288;178573287;178573286	chr2:179438015;179438014;179438013
Novex-1	15342	46249;46250;46251	chr2:178573288;178573287;178573286	chr2:179438015;179438014;179438013
Novex-2	15409	46450;46451;46452	chr2:178573288;178573287;178573286	chr2:179438015;179438014;179438013
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-64
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.1689
• 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
Y/H	rs369711272	-1.316	0.741	N	0.451	0.384	None	gnomAD-2.1.1	1.74E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.86E-05	2.81E-05	0
Y/H	rs369711272	-1.316	0.741	N	0.451	0.384	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
Y/H	rs369711272	-1.316	0.741	N	0.451	0.384	None	gnomAD-4.0.0	8.80585E-06	None	None	None	None	N	None	0	3.56544E-05	None	0	0	None	1.57858E-05	0	9.41473E-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
Y/A	0.6837	likely_pathogenic	0.6349	pathogenic	-2.325	Highly Destabilizing	0.149	N	0.531	neutral	None	None	None	None	N
Y/C	0.1049	likely_benign	0.0876	benign	-1.268	Destabilizing	0.915	D	0.611	neutral	N	0.485622596	None	None	N
Y/D	0.8162	likely_pathogenic	0.7631	pathogenic	-2.017	Highly Destabilizing	0.741	D	0.624	neutral	D	0.526334022	None	None	N
Y/E	0.865	likely_pathogenic	0.83	pathogenic	-1.87	Destabilizing	0.555	D	0.578	neutral	None	None	None	None	N
Y/F	0.0689	likely_benign	0.0665	benign	-0.763	Destabilizing	None	N	0.158	neutral	N	0.424534065	None	None	N
Y/G	0.6612	likely_pathogenic	0.6082	pathogenic	-2.685	Highly Destabilizing	0.262	N	0.609	neutral	None	None	None	None	N
Y/H	0.2846	likely_benign	0.25	benign	-1.166	Destabilizing	0.741	D	0.451	neutral	N	0.475032997	None	None	N
Y/I	0.4592	ambiguous	0.41	ambiguous	-1.187	Destabilizing	0.081	N	0.471	neutral	None	None	None	None	N
Y/K	0.8158	likely_pathogenic	0.7801	pathogenic	-1.78	Destabilizing	0.555	D	0.58	neutral	None	None	None	None	N
Y/L	0.3377	likely_benign	0.3001	benign	-1.187	Destabilizing	0.001	N	0.294	neutral	None	None	None	None	N
Y/M	0.5185	ambiguous	0.4829	ambiguous	-0.889	Destabilizing	0.38	N	0.521	neutral	None	None	None	None	N
Y/N	0.5079	ambiguous	0.4327	ambiguous	-2.431	Highly Destabilizing	0.741	D	0.597	neutral	D	0.526080532	None	None	N
Y/P	0.9887	likely_pathogenic	0.981	pathogenic	-1.569	Destabilizing	0.791	D	0.646	neutral	None	None	None	None	N
Y/Q	0.6565	likely_pathogenic	0.6031	pathogenic	-2.225	Highly Destabilizing	0.791	D	0.525	neutral	None	None	None	None	N
Y/R	0.7207	likely_pathogenic	0.6748	pathogenic	-1.488	Destabilizing	0.555	D	0.594	neutral	None	None	None	None	N
Y/S	0.502	ambiguous	0.4372	ambiguous	-2.801	Highly Destabilizing	0.211	N	0.575	neutral	N	0.478262227	None	None	N
Y/T	0.6964	likely_pathogenic	0.653	pathogenic	-2.549	Highly Destabilizing	0.262	N	0.575	neutral	None	None	None	None	N
Y/V	0.3714	ambiguous	0.3346	benign	-1.569	Destabilizing	0.081	N	0.487	neutral	None	None	None	None	N
Y/W	0.441	ambiguous	0.4082	ambiguous	-0.309	Destabilizing	0.555	D	0.453	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.