TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34347	103264;103265;103266	chr2:178533576;178533575;178533574	chr2:179398303;179398302;179398301
N2AB	32706	98341;98342;98343	chr2:178533576;178533575;178533574	chr2:179398303;179398302;179398301
N2A	31779	95560;95561;95562	chr2:178533576;178533575;178533574	chr2:179398303;179398302;179398301
N2B	25282	76069;76070;76071	chr2:178533576;178533575;178533574	chr2:179398303;179398302;179398301
Novex-1	25407	76444;76445;76446	chr2:178533576;178533575;178533574	chr2:179398303;179398302;179398301
Novex-2	25474	76645;76646;76647	chr2:178533576;178533575;178533574	chr2:179398303;179398302;179398301
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-161
• Domain position: 90
• Structural Position: 173
• Q(SASA): 0.2275
• 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	rs1187906800	None	0.011	N	0.129	0.178	0.30212335484	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92234E-04	None	0	0	0	0	0
K/R	rs1187906800	None	0.011	N	0.129	0.178	0.30212335484	gnomAD-4.0.0	6.56901E-06	None	None	None	None	N	None	0	0	None	0	1.92234E-04	None	0	0	0	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	0.5633	ambiguous	0.4952	ambiguous	-0.722	Destabilizing	0.919	D	0.553	neutral	None	None	None	None	N
K/C	0.7952	likely_pathogenic	0.752	pathogenic	-0.873	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.8601	likely_pathogenic	0.8252	pathogenic	-0.675	Destabilizing	0.851	D	0.575	neutral	None	None	None	None	N
K/E	0.3846	ambiguous	0.3191	benign	-0.554	Destabilizing	0.026	N	0.201	neutral	N	0.441685391	None	None	N
K/F	0.8128	likely_pathogenic	0.7788	pathogenic	-0.508	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	N
K/G	0.7988	likely_pathogenic	0.7473	pathogenic	-1.099	Destabilizing	0.959	D	0.659	neutral	None	None	None	None	N
K/H	0.3362	likely_benign	0.2932	benign	-1.524	Destabilizing	0.988	D	0.684	prob.neutral	None	None	None	None	N
K/I	0.4142	ambiguous	0.379	ambiguous	0.265	Stabilizing	0.988	D	0.723	prob.delet.	None	None	None	None	N
K/L	0.4531	ambiguous	0.4026	ambiguous	0.265	Stabilizing	0.919	D	0.666	neutral	None	None	None	None	N
K/M	0.3219	likely_benign	0.2844	benign	0.252	Stabilizing	0.999	D	0.662	neutral	N	0.495330662	None	None	N
K/N	0.6483	likely_pathogenic	0.5865	pathogenic	-0.808	Destabilizing	0.896	D	0.557	neutral	N	0.439802666	None	None	N
K/P	0.9472	likely_pathogenic	0.9462	pathogenic	-0.034	Destabilizing	0.988	D	0.681	prob.neutral	None	None	None	None	N
K/Q	0.196	likely_benign	0.1679	benign	-0.909	Destabilizing	0.811	D	0.563	neutral	N	0.438282514	None	None	N
K/R	0.0879	likely_benign	0.0826	benign	-0.761	Destabilizing	0.011	N	0.129	neutral	N	0.421659623	None	None	N
K/S	0.6288	likely_pathogenic	0.5728	pathogenic	-1.438	Destabilizing	0.919	D	0.533	neutral	None	None	None	None	N
K/T	0.2583	likely_benign	0.2215	benign	-1.107	Destabilizing	0.896	D	0.617	neutral	N	0.421254191	None	None	N
K/V	0.3907	ambiguous	0.3511	ambiguous	-0.034	Destabilizing	0.988	D	0.687	prob.neutral	None	None	None	None	N
K/W	0.821	likely_pathogenic	0.7887	pathogenic	-0.411	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/Y	0.708	likely_pathogenic	0.6677	pathogenic	-0.063	Destabilizing	0.996	D	0.718	prob.delet.	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.