TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2253	6982;6983;6984	chr2:178774954;178774953;178774952	chr2:179639681;179639680;179639679
N2AB	2253	6982;6983;6984	chr2:178774954;178774953;178774952	chr2:179639681;179639680;179639679
N2A	2253	6982;6983;6984	chr2:178774954;178774953;178774952	chr2:179639681;179639680;179639679
N2B	2207	6844;6845;6846	chr2:178774954;178774953;178774952	chr2:179639681;179639680;179639679
Novex-1	2207	6844;6845;6846	chr2:178774954;178774953;178774952	chr2:179639681;179639680;179639679
Novex-2	2207	6844;6845;6846	chr2:178774954;178774953;178774952	chr2:179639681;179639680;179639679
Novex-3	2253	6982;6983;6984	chr2:178774954;178774953;178774952	chr2:179639681;179639680;179639679

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-11
• Domain position: 80
• Structural Position: 165
• Q(SASA): 0.3532
• 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
N/K	rs1296864074	-0.188	0.183	N	0.324	0.114	0.0611884634855	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	0	0	None	0	1.09051E-04	None	0	None	0	0	0
N/K	rs1296864074	-0.188	0.183	N	0.324	0.114	0.0611884634855	gnomAD-4.0.0	3.18242E-06	None	None	None	None	N	None	0	0	None	0	5.55247E-05	None	0	0	0	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
N/A	0.1115	likely_benign	0.1119	benign	-0.059	Destabilizing	0.129	N	0.589	neutral	None	None	None	None	N
N/C	0.2325	likely_benign	0.2358	benign	0.207	Stabilizing	0.983	D	0.629	neutral	None	None	None	None	N
N/D	0.0988	likely_benign	0.0981	benign	0.077	Stabilizing	0.002	N	0.118	neutral	N	0.454284187	None	None	N
N/E	0.181	likely_benign	0.1826	benign	0.019	Stabilizing	0.01	N	0.131	neutral	None	None	None	None	N
N/F	0.2949	likely_benign	0.3064	benign	-0.63	Destabilizing	0.836	D	0.649	neutral	None	None	None	None	N
N/G	0.1593	likely_benign	0.1652	benign	-0.164	Destabilizing	0.129	N	0.367	neutral	None	None	None	None	N
N/H	0.0877	likely_benign	0.0884	benign	-0.182	Destabilizing	0.004	N	0.255	neutral	N	0.435036471	None	None	N
N/I	0.1502	likely_benign	0.1514	benign	0.119	Stabilizing	0.794	D	0.642	neutral	N	0.51019007	None	None	N
N/K	0.1427	likely_benign	0.1479	benign	0.1	Stabilizing	0.183	N	0.324	neutral	N	0.427814228	None	None	N
N/L	0.1468	likely_benign	0.1521	benign	0.119	Stabilizing	0.418	N	0.593	neutral	None	None	None	None	N
N/M	0.1759	likely_benign	0.1753	benign	0.156	Stabilizing	0.983	D	0.611	neutral	None	None	None	None	N
N/P	0.5554	ambiguous	0.5809	pathogenic	0.083	Stabilizing	0.836	D	0.592	neutral	None	None	None	None	N
N/Q	0.1719	likely_benign	0.1794	benign	-0.222	Destabilizing	0.418	N	0.399	neutral	None	None	None	None	N
N/R	0.1757	likely_benign	0.1905	benign	0.172	Stabilizing	0.418	N	0.399	neutral	None	None	None	None	N
N/S	0.0689	likely_benign	0.0689	benign	-0.003	Destabilizing	0.001	N	0.111	neutral	N	0.403529946	None	None	N
N/T	0.0762	likely_benign	0.0747	benign	0.05	Stabilizing	0.101	N	0.337	neutral	N	0.450445291	None	None	N
N/V	0.1537	likely_benign	0.1532	benign	0.083	Stabilizing	0.418	N	0.59	neutral	None	None	None	None	N
N/W	0.5526	ambiguous	0.5666	pathogenic	-0.766	Destabilizing	0.983	D	0.656	neutral	None	None	None	None	N
N/Y	0.1164	likely_benign	0.12	benign	-0.441	Destabilizing	0.655	D	0.631	neutral	N	0.51019007	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.