TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7760	23503;23504;23505	chr2:178720484;178720483;178720482	chr2:179585211;179585210;179585209
N2AB	7443	22552;22553;22554	chr2:178720484;178720483;178720482	chr2:179585211;179585210;179585209
N2A	6516	19771;19772;19773	chr2:178720484;178720483;178720482	chr2:179585211;179585210;179585209
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-62
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2937
• 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
H/P	rs1577994546	None	0.997	N	0.58	0.58	0.645372302287	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/P	rs1577994546	None	0.997	N	0.58	0.58	0.645372302287	gnomAD-4.0.0	6.57047E-06	None	None	None	None	N	None	2.41161E-05	0	None	0	0	None	0	0	0	0	0
H/R	rs1577994546	None	0.952	N	0.489	0.348	0.278143212241	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
H/Y	rs759847053	0.89	0.998	N	0.534	0.3	0.415564226483	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
H/Y	rs759847053	0.89	0.998	N	0.534	0.3	0.415564226483	gnomAD-4.0.0	4.78991E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.11632E-05	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
H/A	0.6215	likely_pathogenic	0.6602	pathogenic	-1.384	Destabilizing	0.985	D	0.525	neutral	None	None	None	None	N
H/C	0.4264	ambiguous	0.4344	ambiguous	-0.613	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
H/D	0.6831	likely_pathogenic	0.7085	pathogenic	-1.041	Destabilizing	0.045	N	0.34	neutral	D	0.531056602	None	None	N
H/E	0.5863	likely_pathogenic	0.6082	pathogenic	-0.894	Destabilizing	0.134	N	0.297	neutral	None	None	None	None	N
H/F	0.5203	ambiguous	0.5346	ambiguous	0.184	Stabilizing	0.999	D	0.573	neutral	None	None	None	None	N
H/G	0.7843	likely_pathogenic	0.8075	pathogenic	-1.78	Destabilizing	0.985	D	0.528	neutral	None	None	None	None	N
H/I	0.4891	ambiguous	0.5223	ambiguous	-0.251	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
H/K	0.5341	ambiguous	0.5655	pathogenic	-1.104	Destabilizing	0.964	D	0.504	neutral	None	None	None	None	N
H/L	0.2258	likely_benign	0.2445	benign	-0.251	Destabilizing	0.993	D	0.585	neutral	N	0.47173894	None	None	N
H/M	0.691	likely_pathogenic	0.7129	pathogenic	-0.43	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	N
H/N	0.2525	likely_benign	0.2751	benign	-1.34	Destabilizing	0.938	D	0.525	neutral	N	0.510854688	None	None	N
H/P	0.9175	likely_pathogenic	0.9082	pathogenic	-0.613	Destabilizing	0.997	D	0.58	neutral	N	0.502075518	None	None	N
H/Q	0.3278	likely_benign	0.3549	ambiguous	-0.983	Destabilizing	0.954	D	0.483	neutral	N	0.441456105	None	None	N
H/R	0.223	likely_benign	0.2444	benign	-1.487	Destabilizing	0.952	D	0.489	neutral	N	0.466503691	None	None	N
H/S	0.504	ambiguous	0.5475	ambiguous	-1.464	Destabilizing	0.985	D	0.512	neutral	None	None	None	None	N
H/T	0.5349	ambiguous	0.571	pathogenic	-1.211	Destabilizing	0.976	D	0.547	neutral	None	None	None	None	N
H/V	0.4277	ambiguous	0.4554	ambiguous	-0.613	Destabilizing	0.995	D	0.59	neutral	None	None	None	None	N
H/W	0.6617	likely_pathogenic	0.649	pathogenic	0.582	Stabilizing	1.0	D	0.614	neutral	None	None	None	None	N
H/Y	0.1808	likely_benign	0.1818	benign	0.561	Stabilizing	0.998	D	0.534	neutral	N	0.511028046	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.