TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22801	68626;68627;68628	chr2:178578114;178578113;178578112	chr2:179442841;179442840;179442839
N2AB	21160	63703;63704;63705	chr2:178578114;178578113;178578112	chr2:179442841;179442840;179442839
N2A	20233	60922;60923;60924	chr2:178578114;178578113;178578112	chr2:179442841;179442840;179442839
N2B	13736	41431;41432;41433	chr2:178578114;178578113;178578112	chr2:179442841;179442840;179442839
Novex-1	13861	41806;41807;41808	chr2:178578114;178578113;178578112	chr2:179442841;179442840;179442839
Novex-2	13928	42007;42008;42009	chr2:178578114;178578113;178578112	chr2:179442841;179442840;179442839
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-53
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.5567
• 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
R/G	rs1465137040	-1.389	0.117	N	0.453	0.172	0.377976839388	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/G	rs1465137040	-1.389	0.117	N	0.453	0.172	0.377976839388	gnomAD-4.0.0	1.59241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86049E-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
R/A	0.3563	ambiguous	0.3712	ambiguous	-0.995	Destabilizing	0.035	N	0.403	neutral	None	None	None	None	N
R/C	0.2205	likely_benign	0.2392	benign	-0.885	Destabilizing	0.935	D	0.46	neutral	None	None	None	None	N
R/D	0.6957	likely_pathogenic	0.6954	pathogenic	-0.557	Destabilizing	0.149	N	0.46	neutral	None	None	None	None	N
R/E	0.3398	likely_benign	0.3449	ambiguous	-0.353	Destabilizing	0.035	N	0.416	neutral	None	None	None	None	N
R/F	0.7297	likely_pathogenic	0.7042	pathogenic	-0.389	Destabilizing	0.791	D	0.475	neutral	None	None	None	None	N
R/G	0.2195	likely_benign	0.2298	benign	-1.368	Destabilizing	0.117	N	0.453	neutral	N	0.466071958	None	None	N
R/H	0.1558	likely_benign	0.1584	benign	-1.654	Destabilizing	0.555	D	0.541	neutral	None	None	None	None	N
R/I	0.454	ambiguous	0.4349	ambiguous	0.048	Stabilizing	0.484	N	0.489	neutral	N	0.504354711	None	None	N
R/K	0.0576	likely_benign	0.0546	benign	-0.706	Destabilizing	None	N	0.223	neutral	N	0.433417333	None	None	N
R/L	0.2774	likely_benign	0.277	benign	0.048	Stabilizing	0.149	N	0.453	neutral	None	None	None	None	N
R/M	0.2615	likely_benign	0.2619	benign	-0.495	Destabilizing	0.791	D	0.502	neutral	None	None	None	None	N
R/N	0.4788	ambiguous	0.4882	ambiguous	-0.719	Destabilizing	0.149	N	0.427	neutral	None	None	None	None	N
R/P	0.4312	ambiguous	0.465	ambiguous	-0.281	Destabilizing	0.262	N	0.488	neutral	None	None	None	None	N
R/Q	0.1078	likely_benign	0.1135	benign	-0.611	Destabilizing	0.081	N	0.439	neutral	None	None	None	None	N
R/S	0.4475	ambiguous	0.4598	ambiguous	-1.34	Destabilizing	0.027	N	0.417	neutral	N	0.46970342	None	None	N
R/T	0.1823	likely_benign	0.2026	benign	-0.917	Destabilizing	0.117	N	0.426	neutral	N	0.332364904	None	None	N
R/V	0.4532	ambiguous	0.4399	ambiguous	-0.281	Destabilizing	0.149	N	0.489	neutral	None	None	None	None	N
R/W	0.3244	likely_benign	0.3261	benign	-0.072	Destabilizing	0.935	D	0.459	neutral	None	None	None	None	N
R/Y	0.5637	ambiguous	0.5521	ambiguous	0.134	Stabilizing	0.555	D	0.495	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.