TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20211	60856;60857;60858	chr2:178591094;178591093;178591092	chr2:179455821;179455820;179455819
N2AB	18570	55933;55934;55935	chr2:178591094;178591093;178591092	chr2:179455821;179455820;179455819
N2A	17643	53152;53153;53154	chr2:178591094;178591093;178591092	chr2:179455821;179455820;179455819
N2B	11146	33661;33662;33663	chr2:178591094;178591093;178591092	chr2:179455821;179455820;179455819
Novex-1	11271	34036;34037;34038	chr2:178591094;178591093;178591092	chr2:179455821;179455820;179455819
Novex-2	11338	34237;34238;34239	chr2:178591094;178591093;178591092	chr2:179455821;179455820;179455819
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: Fn3-34
• Domain position: 41
• Structural Position: 42
• Q(SASA): 0.3108
• 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	rs760080560	-1.897	1.0	N	0.837	0.539	0.395595088485	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
K/T	rs760080560	-1.897	1.0	N	0.837	0.539	0.395595088485	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85979E-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	0.9419	likely_pathogenic	0.9586	pathogenic	-1.326	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
K/C	0.8929	likely_pathogenic	0.9064	pathogenic	-1.211	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/D	0.9951	likely_pathogenic	0.9963	pathogenic	-1.524	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
K/E	0.8718	likely_pathogenic	0.916	pathogenic	-1.214	Destabilizing	0.999	D	0.765	deleterious	N	0.515984312	None	None	N
K/F	0.9539	likely_pathogenic	0.9665	pathogenic	-0.697	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
K/G	0.9623	likely_pathogenic	0.9715	pathogenic	-1.803	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
K/H	0.7621	likely_pathogenic	0.7986	pathogenic	-1.404	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/I	0.7974	likely_pathogenic	0.8325	pathogenic	0.034	Stabilizing	1.0	D	0.873	deleterious	N	0.471658273	None	None	N
K/L	0.7718	likely_pathogenic	0.8031	pathogenic	0.034	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
K/M	0.5194	ambiguous	0.5832	pathogenic	-0.312	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/N	0.9722	likely_pathogenic	0.9803	pathogenic	-1.486	Destabilizing	1.0	D	0.865	deleterious	N	0.515984312	None	None	N
K/P	0.998	likely_pathogenic	0.9986	pathogenic	-0.4	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
K/Q	0.4327	ambiguous	0.5242	ambiguous	-1.14	Destabilizing	1.0	D	0.861	deleterious	N	0.478129961	None	None	N
K/R	0.1395	likely_benign	0.1644	benign	-0.398	Destabilizing	0.999	D	0.739	prob.delet.	N	0.509187315	None	None	N
K/S	0.9612	likely_pathogenic	0.9734	pathogenic	-2.096	Highly Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
K/T	0.8308	likely_pathogenic	0.8711	pathogenic	-1.513	Destabilizing	1.0	D	0.837	deleterious	N	0.485256304	None	None	N
K/V	0.7904	likely_pathogenic	0.8284	pathogenic	-0.4	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
K/W	0.9395	likely_pathogenic	0.9577	pathogenic	-0.662	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/Y	0.8526	likely_pathogenic	0.8809	pathogenic	-0.325	Destabilizing	1.0	D	0.849	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.