TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31915	95968;95969;95970	chr2:178544486;178544485;178544484	chr2:179409213;179409212;179409211
N2AB	30274	91045;91046;91047	chr2:178544486;178544485;178544484	chr2:179409213;179409212;179409211
N2A	29347	88264;88265;88266	chr2:178544486;178544485;178544484	chr2:179409213;179409212;179409211
N2B	22850	68773;68774;68775	chr2:178544486;178544485;178544484	chr2:179409213;179409212;179409211
Novex-1	22975	69148;69149;69150	chr2:178544486;178544485;178544484	chr2:179409213;179409212;179409211
Novex-2	23042	69349;69350;69351	chr2:178544486;178544485;178544484	chr2:179409213;179409212;179409211
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-121
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.58
• 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/S	rs1490243211	-0.403	None	N	0.212	0.104	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66945E-04
A/S	rs1490243211	-0.403	None	N	0.212	0.104	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	0	2.61849E-04	0	0	0	None	0	0	0	0	0
A/S	rs1490243211	-0.403	None	N	0.212	0.104	None	gnomAD-4.0.0	6.85325E-06	None	None	None	None	I	None	0	1.00164E-04	None	0	0	None	0	0	4.2642E-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
A/C	0.3049	likely_benign	0.3256	benign	-1.156	Destabilizing	0.824	D	0.437	neutral	None	None	None	None	I
A/D	0.3427	ambiguous	0.3354	benign	-1.295	Destabilizing	0.188	N	0.464	neutral	N	0.43237997	None	None	I
A/E	0.2683	likely_benign	0.2499	benign	-1.307	Destabilizing	0.081	N	0.447	neutral	None	None	None	None	I
A/F	0.2169	likely_benign	0.226	benign	-1.133	Destabilizing	0.38	N	0.457	neutral	None	None	None	None	I
A/G	0.1433	likely_benign	0.1472	benign	-1.324	Destabilizing	0.062	N	0.311	neutral	N	0.458507778	None	None	I
A/H	0.3552	ambiguous	0.3548	ambiguous	-1.42	Destabilizing	0.824	D	0.387	neutral	None	None	None	None	I
A/I	0.1245	likely_benign	0.1267	benign	-0.476	Destabilizing	None	N	0.215	neutral	None	None	None	None	I
A/K	0.3478	ambiguous	0.3205	benign	-1.19	Destabilizing	0.081	N	0.444	neutral	None	None	None	None	I
A/L	0.1044	likely_benign	0.1126	benign	-0.476	Destabilizing	0.016	N	0.423	neutral	None	None	None	None	I
A/M	0.1368	likely_benign	0.1429	benign	-0.488	Destabilizing	0.016	N	0.434	neutral	None	None	None	None	I
A/N	0.1987	likely_benign	0.2146	benign	-0.997	Destabilizing	0.235	N	0.459	neutral	None	None	None	None	I
A/P	0.1275	likely_benign	0.106	benign	-0.63	Destabilizing	0.317	N	0.499	neutral	N	0.438596653	None	None	I
A/Q	0.2613	likely_benign	0.2528	benign	-1.152	Destabilizing	0.38	N	0.469	neutral	None	None	None	None	I
A/R	0.3424	ambiguous	0.3133	benign	-0.886	Destabilizing	0.38	N	0.502	neutral	None	None	None	None	I
A/S	0.0857	likely_benign	0.0923	benign	-1.398	Destabilizing	None	N	0.212	neutral	N	0.440404807	None	None	I
A/T	0.0769	likely_benign	0.0768	benign	-1.312	Destabilizing	0.002	N	0.257	neutral	N	0.465089821	None	None	I
A/V	0.0805	likely_benign	0.0805	benign	-0.63	Destabilizing	None	N	0.085	neutral	N	0.493257857	None	None	I
A/W	0.633	likely_pathogenic	0.6404	pathogenic	-1.447	Destabilizing	0.935	D	0.5	neutral	None	None	None	None	I
A/Y	0.3096	likely_benign	0.3272	benign	-1.044	Destabilizing	0.555	D	0.44	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.