TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22703	68332;68333;68334	chr2:178578923;178578922;178578921	chr2:179443650;179443649;179443648
N2AB	21062	63409;63410;63411	chr2:178578923;178578922;178578921	chr2:179443650;179443649;179443648
N2A	20135	60628;60629;60630	chr2:178578923;178578922;178578921	chr2:179443650;179443649;179443648
N2B	13638	41137;41138;41139	chr2:178578923;178578922;178578921	chr2:179443650;179443649;179443648
Novex-1	13763	41512;41513;41514	chr2:178578923;178578922;178578921	chr2:179443650;179443649;179443648
Novex-2	13830	41713;41714;41715	chr2:178578923;178578922;178578921	chr2:179443650;179443649;179443648
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-52
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.2297
• 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	rs2047065698	None	0.999	N	0.583	0.488	0.687538048876	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
F/C	rs2047065698	None	0.999	N	0.583	0.488	0.687538048876	gnomAD-4.0.0	6.58068E-06	None	None	None	None	N	None	0	6.55824E-05	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	0.8744	likely_pathogenic	0.8592	pathogenic	-2.288	Highly Destabilizing	0.939	D	0.534	neutral	None	None	None	None	N
F/C	0.4091	ambiguous	0.3583	ambiguous	-1.553	Destabilizing	0.999	D	0.583	neutral	N	0.440367522	None	None	N
F/D	0.9902	likely_pathogenic	0.9879	pathogenic	-1.753	Destabilizing	0.997	D	0.605	neutral	None	None	None	None	N
F/E	0.9833	likely_pathogenic	0.9825	pathogenic	-1.595	Destabilizing	0.997	D	0.609	neutral	None	None	None	None	N
F/G	0.9531	likely_pathogenic	0.948	pathogenic	-2.677	Highly Destabilizing	0.969	D	0.581	neutral	None	None	None	None	N
F/H	0.8603	likely_pathogenic	0.8316	pathogenic	-0.934	Destabilizing	0.991	D	0.518	neutral	None	None	None	None	N
F/I	0.481	ambiguous	0.4615	ambiguous	-1.069	Destabilizing	0.852	D	0.438	neutral	N	0.49085227	None	None	N
F/K	0.9759	likely_pathogenic	0.9771	pathogenic	-1.797	Destabilizing	0.991	D	0.608	neutral	None	None	None	None	N
F/L	0.9216	likely_pathogenic	0.9043	pathogenic	-1.069	Destabilizing	0.509	D	0.389	neutral	N	0.475997461	None	None	N
F/M	0.5762	likely_pathogenic	0.6232	pathogenic	-0.862	Destabilizing	0.373	N	0.234	neutral	None	None	None	None	N
F/N	0.9439	likely_pathogenic	0.9413	pathogenic	-2.144	Highly Destabilizing	0.997	D	0.609	neutral	None	None	None	None	N
F/P	0.9992	likely_pathogenic	0.999	pathogenic	-1.476	Destabilizing	0.997	D	0.624	neutral	None	None	None	None	N
F/Q	0.9388	likely_pathogenic	0.9403	pathogenic	-2.092	Highly Destabilizing	0.991	D	0.607	neutral	None	None	None	None	N
F/R	0.9502	likely_pathogenic	0.9494	pathogenic	-1.265	Destabilizing	0.991	D	0.603	neutral	None	None	None	None	N
F/S	0.8565	likely_pathogenic	0.8274	pathogenic	-2.869	Highly Destabilizing	0.959	D	0.51	neutral	N	0.478827977	None	None	N
F/T	0.8896	likely_pathogenic	0.8879	pathogenic	-2.603	Highly Destabilizing	0.969	D	0.532	neutral	None	None	None	None	N
F/V	0.4534	ambiguous	0.4284	ambiguous	-1.476	Destabilizing	0.704	D	0.473	neutral	N	0.477341468	None	None	N
F/W	0.7297	likely_pathogenic	0.687	pathogenic	-0.131	Destabilizing	0.997	D	0.449	neutral	None	None	None	None	N
F/Y	0.2265	likely_benign	0.1804	benign	-0.459	Destabilizing	0.134	N	0.225	neutral	N	0.42479785	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.