TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18178	54757;54758;54759	chr2:178604155;178604154;178604153	chr2:179468882;179468881;179468880
N2AB	16537	49834;49835;49836	chr2:178604155;178604154;178604153	chr2:179468882;179468881;179468880
N2A	15610	47053;47054;47055	chr2:178604155;178604154;178604153	chr2:179468882;179468881;179468880
N2B	9113	27562;27563;27564	chr2:178604155;178604154;178604153	chr2:179468882;179468881;179468880
Novex-1	9238	27937;27938;27939	chr2:178604155;178604154;178604153	chr2:179468882;179468881;179468880
Novex-2	9305	28138;28139;28140	chr2:178604155;178604154;178604153	chr2:179468882;179468881;179468880
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-20
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.3322
• 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/C	rs554701601	-0.893	0.031	N	0.272	0.19	0.264081493735	gnomAD-2.1.1	2.51E-05	None	None	None	None	N	None	0	2.84E-05	None	0	0	None	6.56E-05	None	0	3.14E-05	0
R/C	rs554701601	-0.893	0.031	N	0.272	0.19	0.264081493735	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	2.94E-05	2.06782E-04	0
R/C	rs554701601	-0.893	0.031	N	0.272	0.19	0.264081493735	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	1E-03	None
R/C	rs554701601	-0.893	0.031	N	0.272	0.19	0.264081493735	gnomAD-4.0.0	2.48118E-05	None	None	None	None	N	None	0	3.34024E-05	None	0	2.23684E-05	None	0	0	2.71435E-05	5.50031E-05	0
R/G	None	None	0.82	N	0.435	0.205	0.347659731818	gnomAD-4.0.0	6.84881E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87406E-05	0	0	0	0
R/H	rs879023208	-1.74	0.031	N	0.185	0.146	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	1.0022E-04	0	None	0	None	0	0	0
R/H	rs879023208	-1.74	0.031	N	0.185	0.146	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/H	rs879023208	-1.74	0.031	N	0.185	0.146	None	gnomAD-4.0.0	6.82426E-06	None	None	None	None	N	None	1.3374E-05	0	None	3.3873E-05	0	None	0	0	7.63464E-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	0.3932	ambiguous	0.262	benign	-0.802	Destabilizing	0.329	N	0.286	neutral	None	None	None	None	N
R/C	0.16	likely_benign	0.1147	benign	-0.667	Destabilizing	0.031	N	0.272	neutral	N	0.458971925	None	None	N
R/D	0.7652	likely_pathogenic	0.5803	pathogenic	-0.168	Destabilizing	0.704	D	0.535	neutral	None	None	None	None	N
R/E	0.4532	ambiguous	0.3226	benign	-0.037	Destabilizing	0.704	D	0.34	neutral	None	None	None	None	N
R/F	0.5704	likely_pathogenic	0.3715	ambiguous	-0.598	Destabilizing	0.007	N	0.335	neutral	None	None	None	None	N
R/G	0.3275	likely_benign	0.1937	benign	-1.134	Destabilizing	0.82	D	0.435	neutral	N	0.489678834	None	None	N
R/H	0.1346	likely_benign	0.084	benign	-1.487	Destabilizing	0.031	N	0.185	neutral	N	0.494161934	None	None	N
R/I	0.2945	likely_benign	0.2168	benign	0.098	Stabilizing	0.031	N	0.337	neutral	None	None	None	None	N
R/K	0.1065	likely_benign	0.0988	benign	-0.854	Destabilizing	0.495	N	0.349	neutral	None	None	None	None	N
R/L	0.347	ambiguous	0.2239	benign	0.098	Stabilizing	0.291	N	0.265	neutral	N	0.438652581	None	None	N
R/M	0.3909	ambiguous	0.2883	benign	-0.179	Destabilizing	0.944	D	0.484	neutral	None	None	None	None	N
R/N	0.6029	likely_pathogenic	0.4123	ambiguous	-0.304	Destabilizing	0.704	D	0.377	neutral	None	None	None	None	N
R/P	0.617	likely_pathogenic	0.4835	ambiguous	-0.181	Destabilizing	0.99	D	0.577	neutral	N	0.477210969	None	None	N
R/Q	0.1394	likely_benign	0.1011	benign	-0.444	Destabilizing	0.704	D	0.45	neutral	None	None	None	None	N
R/S	0.4892	ambiguous	0.3061	benign	-1.038	Destabilizing	0.82	D	0.421	neutral	N	0.452621956	None	None	N
R/T	0.2535	likely_benign	0.1838	benign	-0.718	Destabilizing	0.704	D	0.419	neutral	None	None	None	None	N
R/V	0.2961	likely_benign	0.2304	benign	-0.181	Destabilizing	0.329	N	0.331	neutral	None	None	None	None	N
R/W	0.3149	likely_benign	0.1835	benign	-0.252	Destabilizing	0.981	D	0.459	neutral	None	None	None	None	N
R/Y	0.4571	ambiguous	0.2778	benign	0.044	Stabilizing	0.013	N	0.267	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.