TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14175	42748;42749;42750	chr2:178633976;178633975;178633974	chr2:179498703;179498702;179498701
N2AB	12534	37825;37826;37827	chr2:178633976;178633975;178633974	chr2:179498703;179498702;179498701
N2A	11607	35044;35045;35046	chr2:178633976;178633975;178633974	chr2:179498703;179498702;179498701
N2B	5110	15553;15554;15555	chr2:178633976;178633975;178633974	chr2:179498703;179498702;179498701
Novex-1	5235	15928;15929;15930	chr2:178633976;178633975;178633974	chr2:179498703;179498702;179498701
Novex-2	5302	16129;16130;16131	chr2:178633976;178633975;178633974	chr2:179498703;179498702;179498701
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-92
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.1413
• 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
F/C	rs575813993	-1.491	0.97	N	0.569	0.295	0.714375579144	gnomAD-2.1.1	4.83E-05	None	None	None	None	N	None	0	2.3183E-04	None	0	0	None	0	None	0	2.67E-05	1.65893E-04
F/C	rs575813993	-1.491	0.97	N	0.569	0.295	0.714375579144	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	1.96799E-04	0	0	0	None	0	0	1.47E-05	0	0
F/C	rs575813993	-1.491	0.97	N	0.569	0.295	0.714375579144	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
F/C	rs575813993	-1.491	0.97	N	0.569	0.295	0.714375579144	gnomAD-4.0.0	5.57838E-05	None	None	None	None	N	None	1.33355E-05	2.16746E-04	None	0	0	None	0	3.30251E-04	5.68026E-05	0	1.12097E-04
F/S	rs575813993	-2.81	0.549	N	0.578	0.27	0.664519762193	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.65399E-04	0	None	0	0	None	0	None	0	0	0
F/S	rs575813993	-2.81	0.549	N	0.578	0.27	0.664519762193	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	2.17213E-04	0	0	0	0	None	0	0	0	0	0
F/S	rs575813993	-2.81	0.549	N	0.578	0.27	0.664519762193	gnomAD-4.0.0	6.81852E-06	None	None	None	None	N	None	1.46929E-04	0	None	0	0	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
F/A	0.8469	likely_pathogenic	0.8789	pathogenic	-2.796	Highly Destabilizing	0.447	N	0.57	neutral	None	None	None	None	N
F/C	0.4588	ambiguous	0.4975	ambiguous	-1.461	Destabilizing	0.97	D	0.569	neutral	N	0.454959534	None	None	N
F/D	0.9271	likely_pathogenic	0.9562	pathogenic	-2.413	Highly Destabilizing	0.972	D	0.629	neutral	None	None	None	None	N
F/E	0.8672	likely_pathogenic	0.9045	pathogenic	-2.284	Highly Destabilizing	0.92	D	0.624	neutral	None	None	None	None	N
F/G	0.8957	likely_pathogenic	0.9302	pathogenic	-3.176	Highly Destabilizing	0.766	D	0.613	neutral	None	None	None	None	N
F/H	0.4921	ambiguous	0.5744	pathogenic	-1.461	Destabilizing	0.85	D	0.599	neutral	None	None	None	None	N
F/I	0.4954	ambiguous	0.4767	ambiguous	-1.593	Destabilizing	0.173	N	0.571	neutral	N	0.47619935	None	None	N
F/K	0.8375	likely_pathogenic	0.8883	pathogenic	-1.684	Destabilizing	0.92	D	0.624	neutral	None	None	None	None	N
F/L	0.8465	likely_pathogenic	0.8673	pathogenic	-1.593	Destabilizing	0.201	N	0.522	neutral	N	0.415707821	None	None	N
F/M	0.6375	likely_pathogenic	0.6529	pathogenic	-1.161	Destabilizing	0.85	D	0.602	neutral	None	None	None	None	N
F/N	0.7151	likely_pathogenic	0.7981	pathogenic	-1.855	Destabilizing	0.92	D	0.627	neutral	None	None	None	None	N
F/P	0.9992	likely_pathogenic	0.9995	pathogenic	-1.998	Destabilizing	0.972	D	0.641	neutral	None	None	None	None	N
F/Q	0.7465	likely_pathogenic	0.8144	pathogenic	-1.96	Destabilizing	0.972	D	0.639	neutral	None	None	None	None	N
F/R	0.7325	likely_pathogenic	0.8106	pathogenic	-0.96	Destabilizing	0.92	D	0.627	neutral	None	None	None	None	N
F/S	0.6536	likely_pathogenic	0.7002	pathogenic	-2.584	Highly Destabilizing	0.549	D	0.578	neutral	N	0.458288059	None	None	N
F/T	0.7595	likely_pathogenic	0.7995	pathogenic	-2.361	Highly Destabilizing	0.617	D	0.565	neutral	None	None	None	None	N
F/V	0.4861	ambiguous	0.4791	ambiguous	-1.998	Destabilizing	0.004	N	0.319	neutral	N	0.45884486	None	None	N
F/W	0.3936	ambiguous	0.4293	ambiguous	-0.602	Destabilizing	0.92	D	0.591	neutral	None	None	None	None	N
F/Y	0.0912	likely_benign	0.1133	benign	-0.899	Destabilizing	0.001	N	0.201	neutral	N	0.362378376	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.