TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29127	87604;87605;87606	chr2:178557975;178557974;178557973	chr2:179422702;179422701;179422700
N2AB	27486	82681;82682;82683	chr2:178557975;178557974;178557973	chr2:179422702;179422701;179422700
N2A	26559	79900;79901;79902	chr2:178557975;178557974;178557973	chr2:179422702;179422701;179422700
N2B	20062	60409;60410;60411	chr2:178557975;178557974;178557973	chr2:179422702;179422701;179422700
Novex-1	20187	60784;60785;60786	chr2:178557975;178557974;178557973	chr2:179422702;179422701;179422700
Novex-2	20254	60985;60986;60987	chr2:178557975;178557974;178557973	chr2:179422702;179422701;179422700
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-145
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.3987
• 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/R	rs1351987923	None	0.01	N	0.289	0.11	0.318252033908	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs1351987923	None	0.01	N	0.289	0.11	0.318252033908	gnomAD-4.0.0	6.57108E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46981E-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
K/A	0.3255	likely_benign	0.2908	benign	-0.104	Destabilizing	0.648	D	0.591	neutral	None	None	None	None	N
K/C	0.6941	likely_pathogenic	0.656	pathogenic	-0.142	Destabilizing	0.993	D	0.78	deleterious	None	None	None	None	N
K/D	0.6166	likely_pathogenic	0.5509	ambiguous	-0.055	Destabilizing	0.866	D	0.781	deleterious	None	None	None	None	N
K/E	0.1756	likely_benign	0.1543	benign	-0.04	Destabilizing	0.41	N	0.503	neutral	N	0.437220934	None	None	N
K/F	0.8644	likely_pathogenic	0.8471	pathogenic	-0.208	Destabilizing	0.98	D	0.765	deleterious	None	None	None	None	N
K/G	0.5041	ambiguous	0.4647	ambiguous	-0.348	Destabilizing	0.866	D	0.677	prob.neutral	None	None	None	None	N
K/H	0.3189	likely_benign	0.2905	benign	-0.719	Destabilizing	0.98	D	0.729	prob.delet.	None	None	None	None	N
K/I	0.4593	ambiguous	0.4436	ambiguous	0.469	Stabilizing	0.908	D	0.787	deleterious	N	0.5147245	None	None	N
K/L	0.4614	ambiguous	0.4447	ambiguous	0.469	Stabilizing	0.866	D	0.677	prob.neutral	None	None	None	None	N
K/M	0.2831	likely_benign	0.2645	benign	0.389	Stabilizing	0.993	D	0.734	prob.delet.	None	None	None	None	N
K/N	0.4499	ambiguous	0.4106	ambiguous	0.143	Stabilizing	0.83	D	0.679	prob.neutral	N	0.484401593	None	None	N
K/P	0.8879	likely_pathogenic	0.8624	pathogenic	0.307	Stabilizing	0.929	D	0.783	deleterious	None	None	None	None	N
K/Q	0.1423	likely_benign	0.1286	benign	-0.072	Destabilizing	0.83	D	0.671	neutral	N	0.483708159	None	None	N
K/R	0.0844	likely_benign	0.0837	benign	-0.172	Destabilizing	0.01	N	0.289	neutral	N	0.476590186	None	None	N
K/S	0.3651	ambiguous	0.3138	benign	-0.371	Destabilizing	0.648	D	0.578	neutral	None	None	None	None	N
K/T	0.135	likely_benign	0.1162	benign	-0.199	Destabilizing	0.83	D	0.731	prob.delet.	N	0.438375727	None	None	N
K/V	0.3314	likely_benign	0.3101	benign	0.307	Stabilizing	0.866	D	0.777	deleterious	None	None	None	None	N
K/W	0.8548	likely_pathogenic	0.835	pathogenic	-0.166	Destabilizing	0.993	D	0.77	deleterious	None	None	None	None	N
K/Y	0.7424	likely_pathogenic	0.7175	pathogenic	0.165	Stabilizing	0.929	D	0.777	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.