TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7718	23377;23378;23379	chr2:178720610;178720609;178720608	chr2:179585337;179585336;179585335
N2AB	7401	22426;22427;22428	chr2:178720610;178720609;178720608	chr2:179585337;179585336;179585335
N2A	6474	19645;19646;19647	chr2:178720610;178720609;178720608	chr2:179585337;179585336;179585335
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-62
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3736
• 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
D/G	rs1216947854	-0.905	0.861	N	0.324	0.278	0.154104182512	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
D/G	rs1216947854	-0.905	0.861	N	0.324	0.278	0.154104182512	gnomAD-4.0.0	4.10825E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39864E-06	0	0
D/N	None	None	0.111	N	0.189	0.146	0.0954503805726	gnomAD-4.0.0	6.84766E-07	None	None	None	None	N	None	2.99904E-05	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
D/A	0.6415	likely_pathogenic	0.5761	pathogenic	-0.425	Destabilizing	0.218	N	0.293	neutral	N	0.506271935	None	None	N
D/C	0.9678	likely_pathogenic	0.9561	pathogenic	-0.115	Destabilizing	0.998	D	0.445	neutral	None	None	None	None	N
D/E	0.4969	ambiguous	0.4877	ambiguous	-0.481	Destabilizing	0.007	N	0.181	neutral	N	0.467694904	None	None	N
D/F	0.9718	likely_pathogenic	0.9616	pathogenic	-0.075	Destabilizing	1.0	D	0.442	neutral	None	None	None	None	N
D/G	0.707	likely_pathogenic	0.6596	pathogenic	-0.724	Destabilizing	0.861	D	0.324	neutral	N	0.486331217	None	None	N
D/H	0.8033	likely_pathogenic	0.77	pathogenic	-0.206	Destabilizing	0.995	D	0.386	neutral	N	0.473102034	None	None	N
D/I	0.932	likely_pathogenic	0.9046	pathogenic	0.344	Stabilizing	0.999	D	0.445	neutral	None	None	None	None	N
D/K	0.9229	likely_pathogenic	0.9057	pathogenic	-0.027	Destabilizing	0.98	D	0.303	neutral	None	None	None	None	N
D/L	0.9188	likely_pathogenic	0.9004	pathogenic	0.344	Stabilizing	0.99	D	0.379	neutral	None	None	None	None	N
D/M	0.9667	likely_pathogenic	0.9568	pathogenic	0.626	Stabilizing	1.0	D	0.438	neutral	None	None	None	None	N
D/N	0.2695	likely_benign	0.2372	benign	-0.52	Destabilizing	0.111	N	0.189	neutral	N	0.474794235	None	None	N
D/P	0.9201	likely_pathogenic	0.9062	pathogenic	0.112	Stabilizing	0.933	D	0.372	neutral	None	None	None	None	N
D/Q	0.8704	likely_pathogenic	0.8541	pathogenic	-0.396	Destabilizing	0.992	D	0.308	neutral	None	None	None	None	N
D/R	0.93	likely_pathogenic	0.9152	pathogenic	0.155	Stabilizing	0.997	D	0.394	neutral	None	None	None	None	N
D/S	0.4106	ambiguous	0.3573	ambiguous	-0.664	Destabilizing	0.518	D	0.153	neutral	None	None	None	None	N
D/T	0.7461	likely_pathogenic	0.6842	pathogenic	-0.416	Destabilizing	0.86	D	0.309	neutral	None	None	None	None	N
D/V	0.8177	likely_pathogenic	0.7596	pathogenic	0.112	Stabilizing	0.929	D	0.375	neutral	N	0.509946958	None	None	N
D/W	0.9942	likely_pathogenic	0.9924	pathogenic	0.12	Stabilizing	1.0	D	0.593	neutral	None	None	None	None	N
D/Y	0.8291	likely_pathogenic	0.7865	pathogenic	0.169	Stabilizing	0.999	D	0.443	neutral	N	0.482318745	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.