TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16001	48226;48227;48228	chr2:178616888;178616887;178616886	chr2:179481615;179481614;179481613
N2AB	14360	43303;43304;43305	chr2:178616888;178616887;178616886	chr2:179481615;179481614;179481613
N2A	13433	40522;40523;40524	chr2:178616888;178616887;178616886	chr2:179481615;179481614;179481613
N2B	6936	21031;21032;21033	chr2:178616888;178616887;178616886	chr2:179481615;179481614;179481613
Novex-1	7061	21406;21407;21408	chr2:178616888;178616887;178616886	chr2:179481615;179481614;179481613
Novex-2	7128	21607;21608;21609	chr2:178616888;178616887;178616886	chr2:179481615;179481614;179481613
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-109
• Domain position: 34
• Structural Position: 55
• Q(SASA): 0.4367
• 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/T	None	None	None	N	0.197	0.186	0.273938319068	gnomAD-4.0.0	6.8462E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99866E-07	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	0.2153	likely_benign	0.2142	benign	-0.102	Destabilizing	0.035	N	0.34	neutral	None	None	None	None	N
K/C	0.5954	likely_pathogenic	0.5976	pathogenic	-0.316	Destabilizing	0.935	D	0.333	neutral	None	None	None	None	N
K/D	0.2841	likely_benign	0.2825	benign	0.146	Stabilizing	0.081	N	0.34	neutral	None	None	None	None	N
K/E	0.1055	likely_benign	0.1079	benign	0.193	Stabilizing	0.027	N	0.362	neutral	N	0.503463507	None	None	N
K/F	0.7167	likely_pathogenic	0.7052	pathogenic	-0.136	Destabilizing	0.555	D	0.331	neutral	None	None	None	None	N
K/G	0.3448	ambiguous	0.3289	benign	-0.354	Destabilizing	0.081	N	0.347	neutral	None	None	None	None	N
K/H	0.2329	likely_benign	0.2441	benign	-0.576	Destabilizing	0.38	N	0.32	neutral	None	None	None	None	N
K/I	0.2764	likely_benign	0.2816	benign	0.499	Stabilizing	0.317	N	0.356	neutral	N	0.514603681	None	None	N
K/L	0.3066	likely_benign	0.312	benign	0.499	Stabilizing	0.081	N	0.357	neutral	None	None	None	None	N
K/M	0.1968	likely_benign	0.2011	benign	0.157	Stabilizing	0.555	D	0.329	neutral	None	None	None	None	N
K/N	0.1946	likely_benign	0.1924	benign	0.032	Stabilizing	None	N	0.152	neutral	N	0.492553404	None	None	N
K/P	0.8728	likely_pathogenic	0.8461	pathogenic	0.328	Stabilizing	0.555	D	0.323	neutral	None	None	None	None	N
K/Q	0.1123	likely_benign	0.1143	benign	-0.054	Destabilizing	None	N	0.163	neutral	N	0.468169833	None	None	N
K/R	0.088	likely_benign	0.0901	benign	-0.146	Destabilizing	0.062	N	0.306	neutral	N	0.510009861	None	None	N
K/S	0.231	likely_benign	0.2255	benign	-0.485	Destabilizing	0.035	N	0.315	neutral	None	None	None	None	N
K/T	0.0919	likely_benign	0.0935	benign	-0.266	Destabilizing	None	N	0.197	neutral	N	0.515456717	None	None	N
K/V	0.2225	likely_benign	0.2287	benign	0.328	Stabilizing	0.081	N	0.373	neutral	None	None	None	None	N
K/W	0.7642	likely_pathogenic	0.7505	pathogenic	-0.138	Destabilizing	0.935	D	0.359	neutral	None	None	None	None	N
K/Y	0.5657	likely_pathogenic	0.5604	ambiguous	0.195	Stabilizing	0.555	D	0.328	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.