TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8055	24388;24389;24390	chr2:178719227;178719226;178719225	chr2:179583954;179583953;179583952
N2AB	7738	23437;23438;23439	chr2:178719227;178719226;178719225	chr2:179583954;179583953;179583952
N2A	6811	20656;20657;20658	chr2:178719227;178719226;178719225	chr2:179583954;179583953;179583952
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-65
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1348
• 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
Y/H	rs1160062455	-2.559	0.999	D	0.729	0.863	0.78574696606	gnomAD-2.1.1	6.37E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.29668E-04	0
Y/H	rs1160062455	-2.559	0.999	D	0.729	0.863	0.78574696606	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
Y/H	rs1160062455	-2.559	0.999	D	0.729	0.863	0.78574696606	gnomAD-4.0.0	6.40561E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.19657E-05	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
Y/A	0.9333	likely_pathogenic	0.948	pathogenic	-2.586	Highly Destabilizing	0.991	D	0.833	deleterious	None	None	None	None	N
Y/C	0.484	ambiguous	0.4481	ambiguous	-1.909	Destabilizing	1.0	D	0.859	deleterious	D	0.664567299	None	None	N
Y/D	0.9806	likely_pathogenic	0.9868	pathogenic	-3.126	Highly Destabilizing	0.999	D	0.882	deleterious	D	0.664567299	None	None	N
Y/E	0.9885	likely_pathogenic	0.9925	pathogenic	-2.876	Highly Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
Y/F	0.0927	likely_benign	0.0892	benign	-0.946	Destabilizing	0.117	N	0.408	neutral	D	0.579000342	None	None	N
Y/G	0.9475	likely_pathogenic	0.9566	pathogenic	-3.053	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
Y/H	0.662	likely_pathogenic	0.7165	pathogenic	-2.228	Highly Destabilizing	0.999	D	0.729	prob.delet.	D	0.648113969	None	None	N
Y/I	0.5913	likely_pathogenic	0.6207	pathogenic	-1.04	Destabilizing	0.99	D	0.803	deleterious	None	None	None	None	N
Y/K	0.9751	likely_pathogenic	0.9828	pathogenic	-2.106	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
Y/L	0.5676	likely_pathogenic	0.6061	pathogenic	-1.04	Destabilizing	0.966	D	0.763	deleterious	None	None	None	None	N
Y/M	0.8399	likely_pathogenic	0.862	pathogenic	-1.092	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
Y/N	0.8573	likely_pathogenic	0.896	pathogenic	-3.037	Highly Destabilizing	0.999	D	0.873	deleterious	D	0.664567299	None	None	N
Y/P	0.9895	likely_pathogenic	0.9898	pathogenic	-1.572	Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
Y/Q	0.953	likely_pathogenic	0.9679	pathogenic	-2.606	Highly Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
Y/R	0.9147	likely_pathogenic	0.9357	pathogenic	-2.255	Highly Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
Y/S	0.833	likely_pathogenic	0.8638	pathogenic	-3.388	Highly Destabilizing	0.997	D	0.87	deleterious	D	0.664567299	None	None	N
Y/T	0.9157	likely_pathogenic	0.932	pathogenic	-2.989	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
Y/V	0.5143	ambiguous	0.5492	ambiguous	-1.572	Destabilizing	0.983	D	0.785	deleterious	None	None	None	None	N
Y/W	0.6178	likely_pathogenic	0.6159	pathogenic	-0.298	Destabilizing	1.0	D	0.718	prob.delet.	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.