TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29349	88270;88271;88272	chr2:178557109;178557108;178557107	chr2:179421836;179421835;179421834
N2AB	27708	83347;83348;83349	chr2:178557109;178557108;178557107	chr2:179421836;179421835;179421834
N2A	26781	80566;80567;80568	chr2:178557109;178557108;178557107	chr2:179421836;179421835;179421834
N2B	20284	61075;61076;61077	chr2:178557109;178557108;178557107	chr2:179421836;179421835;179421834
Novex-1	20409	61450;61451;61452	chr2:178557109;178557108;178557107	chr2:179421836;179421835;179421834
Novex-2	20476	61651;61652;61653	chr2:178557109;178557108;178557107	chr2:179421836;179421835;179421834
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-102
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4413
• 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
K/N	rs748102856	0.051	1.0	N	0.723	0.256	0.206339911435	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
K/N	rs748102856	0.051	1.0	N	0.723	0.256	0.206339911435	gnomAD-4.0.0	1.36857E-06	None	None	None	None	N	None	2.98721E-05	0	None	0	0	None	0	0	0	1.15985E-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
K/A	0.6789	likely_pathogenic	0.6053	pathogenic	-0.179	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	N
K/C	0.8793	likely_pathogenic	0.8529	pathogenic	-0.228	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/D	0.8952	likely_pathogenic	0.8755	pathogenic	-0.31	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
K/E	0.4921	ambiguous	0.4012	ambiguous	-0.308	Destabilizing	0.999	D	0.583	neutral	N	0.495255225	None	None	N
K/F	0.9745	likely_pathogenic	0.9625	pathogenic	-0.548	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
K/G	0.6665	likely_pathogenic	0.6087	pathogenic	-0.397	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/H	0.661	likely_pathogenic	0.6048	pathogenic	-0.915	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/I	0.8563	likely_pathogenic	0.8014	pathogenic	0.323	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/L	0.7877	likely_pathogenic	0.7395	pathogenic	0.323	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/M	0.6784	likely_pathogenic	0.6009	pathogenic	0.514	Stabilizing	1.0	D	0.6	neutral	N	0.505869001	None	None	N
K/N	0.813	likely_pathogenic	0.77	pathogenic	0.093	Stabilizing	1.0	D	0.723	prob.delet.	N	0.508397881	None	None	N
K/P	0.8419	likely_pathogenic	0.8159	pathogenic	0.184	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/Q	0.2823	likely_benign	0.2264	benign	-0.238	Destabilizing	1.0	D	0.715	prob.delet.	N	0.467823612	None	None	N
K/R	0.0824	likely_benign	0.0755	benign	-0.021	Destabilizing	0.999	D	0.532	neutral	N	0.420202893	None	None	N
K/S	0.7405	likely_pathogenic	0.6803	pathogenic	-0.423	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
K/T	0.6191	likely_pathogenic	0.5457	ambiguous	-0.27	Destabilizing	1.0	D	0.689	prob.neutral	N	0.509859319	None	None	N
K/V	0.7806	likely_pathogenic	0.7209	pathogenic	0.184	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/W	0.9512	likely_pathogenic	0.9332	pathogenic	-0.489	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
K/Y	0.9151	likely_pathogenic	0.8924	pathogenic	-0.089	Destabilizing	1.0	D	0.683	prob.neutral	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.