TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25413	76462;76463;76464	chr2:178569895;178569894;178569893	chr2:179434622;179434621;179434620
N2AB	23772	71539;71540;71541	chr2:178569895;178569894;178569893	chr2:179434622;179434621;179434620
N2A	22845	68758;68759;68760	chr2:178569895;178569894;178569893	chr2:179434622;179434621;179434620
N2B	16348	49267;49268;49269	chr2:178569895;178569894;178569893	chr2:179434622;179434621;179434620
Novex-1	16473	49642;49643;49644	chr2:178569895;178569894;178569893	chr2:179434622;179434621;179434620
Novex-2	16540	49843;49844;49845	chr2:178569895;178569894;178569893	chr2:179434622;179434621;179434620
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: Fn3-73
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6621
• 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	None	None	0.001	N	0.335	0.178	0.257786959452	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/R	rs367696053	-0.074	0.001	N	0.206	0.079	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.9E-06	0
K/R	rs367696053	-0.074	0.001	N	0.206	0.079	None	gnomAD-4.0.0	2.05305E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69873E-06	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	0.437	ambiguous	0.432	ambiguous	-0.55	Destabilizing	0.272	N	0.616	neutral	None	None	None	None	N
K/C	0.5714	likely_pathogenic	0.6586	pathogenic	-0.667	Destabilizing	0.968	D	0.783	deleterious	None	None	None	None	N
K/D	0.7577	likely_pathogenic	0.7406	pathogenic	-0.143	Destabilizing	0.157	N	0.648	neutral	None	None	None	None	N
K/E	0.2691	likely_benign	0.2533	benign	0.001	Stabilizing	0.001	N	0.335	neutral	N	0.495586086	None	None	N
K/F	0.7756	likely_pathogenic	0.7994	pathogenic	-0.087	Destabilizing	0.726	D	0.774	deleterious	None	None	None	None	N
K/G	0.5781	likely_pathogenic	0.5842	pathogenic	-0.944	Destabilizing	0.272	N	0.636	neutral	None	None	None	None	N
K/H	0.2523	likely_benign	0.2817	benign	-1.205	Destabilizing	0.909	D	0.703	prob.neutral	None	None	None	None	N
K/I	0.4154	ambiguous	0.4486	ambiguous	0.482	Stabilizing	0.667	D	0.781	deleterious	N	0.480905119	None	None	N
K/L	0.4543	ambiguous	0.4658	ambiguous	0.482	Stabilizing	0.567	D	0.632	neutral	None	None	None	None	N
K/M	0.3156	likely_benign	0.317	benign	0.184	Stabilizing	0.968	D	0.686	prob.neutral	None	None	None	None	N
K/N	0.5622	ambiguous	0.5645	pathogenic	-0.66	Destabilizing	0.497	N	0.583	neutral	N	0.472991854	None	None	N
K/P	0.9673	likely_pathogenic	0.9645	pathogenic	0.168	Stabilizing	0.726	D	0.717	prob.delet.	None	None	None	None	N
K/Q	0.1469	likely_benign	0.1504	benign	-0.619	Destabilizing	0.331	N	0.585	neutral	N	0.501357265	None	None	N
K/R	0.0653	likely_benign	0.0705	benign	-0.711	Destabilizing	0.001	N	0.206	neutral	N	0.470207639	None	None	N
K/S	0.5039	ambiguous	0.5058	ambiguous	-1.278	Destabilizing	0.272	N	0.555	neutral	None	None	None	None	N
K/T	0.2423	likely_benign	0.2418	benign	-0.918	Destabilizing	0.497	N	0.68	prob.neutral	N	0.499509039	None	None	N
K/V	0.3448	ambiguous	0.3618	ambiguous	0.168	Stabilizing	0.567	D	0.685	prob.neutral	None	None	None	None	N
K/W	0.7238	likely_pathogenic	0.7814	pathogenic	-0.007	Destabilizing	0.968	D	0.759	deleterious	None	None	None	None	N
K/Y	0.6328	likely_pathogenic	0.6737	pathogenic	0.278	Stabilizing	0.726	D	0.773	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.