TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23891	71896;71897;71898	chr2:178574461;178574460;178574459	chr2:179439188;179439187;179439186
N2AB	22250	66973;66974;66975	chr2:178574461;178574460;178574459	chr2:179439188;179439187;179439186
N2A	21323	64192;64193;64194	chr2:178574461;178574460;178574459	chr2:179439188;179439187;179439186
N2B	14826	44701;44702;44703	chr2:178574461;178574460;178574459	chr2:179439188;179439187;179439186
Novex-1	14951	45076;45077;45078	chr2:178574461;178574460;178574459	chr2:179439188;179439187;179439186
Novex-2	15018	45277;45278;45279	chr2:178574461;178574460;178574459	chr2:179439188;179439187;179439186
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-61
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.1248
• 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
L/F	None	None	1.0	D	0.867	0.873	0.841522787196	gnomAD-4.0.0	3.18331E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71844E-06	0	0
L/P	None	None	1.0	D	0.835	0.907	0.934807757574	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.9641	likely_pathogenic	0.9536	pathogenic	-2.399	Highly Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
L/C	0.9018	likely_pathogenic	0.8719	pathogenic	-2.39	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9983	pathogenic	-2.519	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/E	0.9935	likely_pathogenic	0.991	pathogenic	-2.413	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/F	0.6377	likely_pathogenic	0.5938	pathogenic	-1.889	Destabilizing	1.0	D	0.867	deleterious	D	0.663815418	None	None	N
L/G	0.9904	likely_pathogenic	0.9868	pathogenic	-2.8	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/H	0.9767	likely_pathogenic	0.9704	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.791	deleterious	D	0.680641996	None	None	N
L/I	0.3237	likely_benign	0.2964	benign	-1.293	Destabilizing	0.999	D	0.82	deleterious	D	0.625427888	None	None	N
L/K	0.9846	likely_pathogenic	0.9824	pathogenic	-1.756	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/M	0.3972	ambiguous	0.3686	ambiguous	-1.393	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/N	0.9868	likely_pathogenic	0.9819	pathogenic	-1.931	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/P	0.9921	likely_pathogenic	0.9886	pathogenic	-1.639	Destabilizing	1.0	D	0.835	deleterious	D	0.680641996	None	None	N
L/Q	0.9639	likely_pathogenic	0.9518	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/R	0.9736	likely_pathogenic	0.9679	pathogenic	-1.225	Destabilizing	1.0	D	0.837	deleterious	D	0.664622635	None	None	N
L/S	0.9915	likely_pathogenic	0.9873	pathogenic	-2.655	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/T	0.9701	likely_pathogenic	0.9604	pathogenic	-2.416	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/V	0.4715	ambiguous	0.4113	ambiguous	-1.639	Destabilizing	0.999	D	0.826	deleterious	D	0.58305248	None	None	N
L/W	0.9622	likely_pathogenic	0.9452	pathogenic	-2.016	Highly Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/Y	0.9578	likely_pathogenic	0.944	pathogenic	-1.757	Destabilizing	1.0	D	0.821	deleterious	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.