TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17052	51379;51380;51381	chr2:178610372;178610371;178610370	chr2:179475099;179475098;179475097
N2AB	15411	46456;46457;46458	chr2:178610372;178610371;178610370	chr2:179475099;179475098;179475097
N2A	14484	43675;43676;43677	chr2:178610372;178610371;178610370	chr2:179475099;179475098;179475097
N2B	7987	24184;24185;24186	chr2:178610372;178610371;178610370	chr2:179475099;179475098;179475097
Novex-1	8112	24559;24560;24561	chr2:178610372;178610371;178610370	chr2:179475099;179475098;179475097
Novex-2	8179	24760;24761;24762	chr2:178610372;178610371;178610370	chr2:179475099;179475098;179475097
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: Fn3-12
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.5448
• 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/E	rs1451084974	None	0.124	N	0.549	0.136	0.250579442822	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	9.5511E-04
K/E	rs1451084974	None	0.124	N	0.549	0.136	0.250579442822	gnomAD-4.0.0	1.31536E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	9.5511E-04

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	0.4502	ambiguous	0.4901	ambiguous	-0.432	Destabilizing	0.272	N	0.615	neutral	None	None	None	None	N
K/C	0.6761	likely_pathogenic	0.7428	pathogenic	-0.226	Destabilizing	0.968	D	0.787	deleterious	None	None	None	None	N
K/D	0.8042	likely_pathogenic	0.8468	pathogenic	-0.21	Destabilizing	0.567	D	0.647	neutral	None	None	None	None	N
K/E	0.3012	likely_benign	0.334	benign	-0.095	Destabilizing	0.124	N	0.549	neutral	N	0.441329462	None	None	N
K/F	0.8707	likely_pathogenic	0.9097	pathogenic	0.071	Stabilizing	0.726	D	0.744	deleterious	None	None	None	None	N
K/G	0.5433	ambiguous	0.5927	pathogenic	-0.816	Destabilizing	0.272	N	0.653	neutral	None	None	None	None	N
K/H	0.3751	ambiguous	0.4184	ambiguous	-1.219	Destabilizing	0.909	D	0.676	prob.neutral	None	None	None	None	N
K/I	0.4494	ambiguous	0.5035	ambiguous	0.575	Stabilizing	0.667	D	0.749	deleterious	N	0.480047592	None	None	N
K/L	0.456	ambiguous	0.5147	ambiguous	0.575	Stabilizing	0.272	N	0.653	neutral	None	None	None	None	N
K/M	0.3425	ambiguous	0.3732	ambiguous	0.389	Stabilizing	0.909	D	0.665	neutral	None	None	None	None	N
K/N	0.5928	likely_pathogenic	0.6383	pathogenic	-0.363	Destabilizing	0.497	N	0.572	neutral	N	0.476429883	None	None	N
K/P	0.9289	likely_pathogenic	0.925	pathogenic	0.269	Stabilizing	0.726	D	0.685	prob.neutral	None	None	None	None	N
K/Q	0.1596	likely_benign	0.1732	benign	-0.353	Destabilizing	0.009	N	0.232	neutral	N	0.448340652	None	None	N
K/R	0.0817	likely_benign	0.0879	benign	-0.775	Destabilizing	0.001	N	0.187	neutral	N	0.45857916	None	None	N
K/S	0.5262	ambiguous	0.5782	pathogenic	-0.879	Destabilizing	0.272	N	0.573	neutral	None	None	None	None	N
K/T	0.2251	likely_benign	0.244	benign	-0.567	Destabilizing	0.497	N	0.656	neutral	N	0.46480257	None	None	N
K/V	0.3893	ambiguous	0.427	ambiguous	0.269	Stabilizing	0.567	D	0.668	neutral	None	None	None	None	N
K/W	0.8441	likely_pathogenic	0.8861	pathogenic	0.12	Stabilizing	0.968	D	0.767	deleterious	None	None	None	None	N
K/Y	0.7758	likely_pathogenic	0.8315	pathogenic	0.357	Stabilizing	0.726	D	0.759	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.