TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3419	10480;10481;10482	chr2:178759032;178759031;178759030	chr2:179623759;179623758;179623757
N2AB	3419	10480;10481;10482	chr2:178759032;178759031;178759030	chr2:179623759;179623758;179623757
N2A	3419	10480;10481;10482	chr2:178759032;178759031;178759030	chr2:179623759;179623758;179623757
N2B	3373	10342;10343;10344	chr2:178759032;178759031;178759030	chr2:179623759;179623758;179623757
Novex-1	3373	10342;10343;10344	chr2:178759032;178759031;178759030	chr2:179623759;179623758;179623757
Novex-2	3373	10342;10343;10344	chr2:178759032;178759031;178759030	chr2:179623759;179623758;179623757
Novex-3	3419	10480;10481;10482	chr2:178759032;178759031;178759030	chr2:179623759;179623758;179623757

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-24
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.259
• 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
S/G	rs1266502582	-1.134	0.012	D	0.373	0.201	0.220303561663	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
S/G	rs1266502582	-1.134	0.012	D	0.373	0.201	0.220303561663	gnomAD-4.0.0	7.52528E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	8.67453E-04	4.49671E-06	0	1.65596E-05
S/N	rs2291310	-0.91	None	D	0.131	0.105	None	gnomAD-2.1.1	8.45905E-01	None	None	None	None	N	None	8.44852E-01	5.72897E-01	None	9.1353E-01	7.69231E-01	None	7.88977E-01	None	8.91751E-01	9.30417E-01	8.75937E-01
S/N	rs2291310	-0.91	None	D	0.131	0.105	None	gnomAD-3.1.2	8.73509E-01	None	None	None	None	N	None	8.44553E-01	7.19651E-01	9.51754E-01	9.18444E-01	7.90621E-01	None	8.91752E-01	9.49367E-01	9.30579E-01	7.90216E-01	8.97608E-01
S/N	rs2291310	-0.91	None	D	0.131	0.105	None	1000 genomes	8.08906E-01	None	None	None	None	N	None	8.389E-01	6.7E-01	None	None	7.847E-01	9.145E-01	None	None	None	7.832E-01	None
S/N	rs2291310	-0.91	None	D	0.131	0.105	None	gnomAD-4.0.0	9.00962E-01	None	None	None	None	N	None	8.45074E-01	6.19775E-01	None	9.16993E-01	7.91436E-01	None	8.89408E-01	9.30175E-01	9.31295E-01	7.95858E-01	8.97709E-01
S/T	rs2291310	None	None	N	0.124	0.071	0.0297737177859	gnomAD-4.0.0	6.84116E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-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
S/A	0.1263	likely_benign	0.1324	benign	-0.654	Destabilizing	None	N	0.124	neutral	None	None	None	None	N
S/C	0.1875	likely_benign	0.1282	benign	-0.613	Destabilizing	0.828	D	0.461	neutral	D	0.652170966	None	None	N
S/D	0.3494	ambiguous	0.2201	benign	-0.788	Destabilizing	0.038	N	0.333	neutral	None	None	None	None	N
S/E	0.4208	ambiguous	0.3734	ambiguous	-0.797	Destabilizing	0.016	N	0.345	neutral	None	None	None	None	N
S/F	0.3897	ambiguous	0.3976	ambiguous	-0.881	Destabilizing	0.356	N	0.561	neutral	None	None	None	None	N
S/G	0.1257	likely_benign	0.1125	benign	-0.888	Destabilizing	0.012	N	0.373	neutral	D	0.56864758	None	None	N
S/H	0.2474	likely_benign	0.1618	benign	-1.414	Destabilizing	0.214	N	0.476	neutral	None	None	None	None	N
S/I	0.2455	likely_benign	0.189	benign	-0.141	Destabilizing	0.171	N	0.555	neutral	N	0.514633406	None	None	N
S/K	0.4991	ambiguous	0.3921	ambiguous	-0.829	Destabilizing	0.001	N	0.175	neutral	None	None	None	None	N
S/L	0.2162	likely_benign	0.2052	benign	-0.141	Destabilizing	0.038	N	0.527	neutral	None	None	None	None	N
S/M	0.3038	likely_benign	0.2758	benign	0.186	Stabilizing	0.628	D	0.475	neutral	None	None	None	None	N
S/N	0.1108	likely_benign	0.0749	benign	-0.84	Destabilizing	None	N	0.131	neutral	D	0.533807268	None	None	N
S/P	0.9541	likely_pathogenic	0.9341	pathogenic	-0.279	Destabilizing	0.136	N	0.463	neutral	None	None	None	None	N
S/Q	0.3746	ambiguous	0.3169	benign	-1.068	Destabilizing	0.072	N	0.397	neutral	None	None	None	None	N
S/R	0.3966	ambiguous	0.3332	benign	-0.648	Destabilizing	None	N	0.344	neutral	N	0.492048096	None	None	N
S/T	0.1011	likely_benign	0.0951	benign	-0.8	Destabilizing	None	N	0.124	neutral	N	0.466791035	None	None	N
S/V	0.2595	likely_benign	0.2265	benign	-0.279	Destabilizing	0.038	N	0.543	neutral	None	None	None	None	N
S/W	0.5304	ambiguous	0.5012	ambiguous	-0.873	Destabilizing	0.864	D	0.593	neutral	None	None	None	None	N
S/Y	0.281	likely_benign	0.2176	benign	-0.597	Destabilizing	0.628	D	0.561	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.