TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3154	9685;9686;9687	chr2:178767770;178767769;178767768	chr2:179632497;179632496;179632495
N2AB	3154	9685;9686;9687	chr2:178767770;178767769;178767768	chr2:179632497;179632496;179632495
N2A	3154	9685;9686;9687	chr2:178767770;178767769;178767768	chr2:179632497;179632496;179632495
N2B	3108	9547;9548;9549	chr2:178767770;178767769;178767768	chr2:179632497;179632496;179632495
Novex-1	3108	9547;9548;9549	chr2:178767770;178767769;178767768	chr2:179632497;179632496;179632495
Novex-2	3108	9547;9548;9549	chr2:178767770;178767769;178767768	chr2:179632497;179632496;179632495
Novex-3	3154	9685;9686;9687	chr2:178767770;178767769;178767768	chr2:179632497;179632496;179632495

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-22
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5936
• 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/N	None	None	0.497	D	0.547	0.324	0.32053947749	gnomAD-4.0.0	6.84118E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99308E-07	0	0
K/R	rs4893853	0.051	None	N	0.157	0.064	None	gnomAD-2.1.1	6.74519E-02	None	None	None	None	N	None	7.07989E-02	1.84945E-01	None	2.91675E-02	2.5439E-02	None	1.69171E-01	None	5.49301E-02	2.30732E-02	5.40915E-02
K/R	rs4893853	0.051	None	N	0.157	0.064	None	gnomAD-3.1.2	5.35297E-02	None	None	None	None	N	None	7.00502E-02	1.34834E-01	0	2.59217E-02	2.17224E-02	None	5.70109E-02	2.8481E-02	2.21373E-02	1.61765E-01	3.77629E-02
K/R	rs4893853	0.051	None	N	0.157	0.064	None	1000 genomes	8.60623E-02	None	None	None	None	N	None	7.49E-02	1.542E-01	None	None	2.08E-02	3.48E-02	None	None	None	1.728E-01	None
K/R	rs4893853	0.051	None	N	0.157	0.064	None	gnomAD-4.0.0	3.99737E-02	None	None	None	None	N	None	6.94148E-02	1.70266E-01	None	2.77646E-02	1.35237E-02	None	5.6435E-02	4.60396E-02	2.2374E-02	1.61495E-01	4.26213E-02

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	0.584	likely_pathogenic	0.5944	pathogenic	0.036	Stabilizing	0.272	N	0.536	neutral	None	None	None	None	N
K/C	0.901	likely_pathogenic	0.8832	pathogenic	-0.307	Destabilizing	0.968	D	0.693	prob.neutral	None	None	None	None	N
K/D	0.6275	likely_pathogenic	0.6195	pathogenic	0.112	Stabilizing	0.567	D	0.573	neutral	None	None	None	None	N
K/E	0.2537	likely_benign	0.2841	benign	0.106	Stabilizing	0.124	N	0.542	neutral	N	0.517655193	None	None	N
K/F	0.9518	likely_pathogenic	0.9584	pathogenic	-0.249	Destabilizing	0.726	D	0.667	neutral	None	None	None	None	N
K/G	0.5377	ambiguous	0.4964	ambiguous	-0.129	Destabilizing	0.272	N	0.54	neutral	None	None	None	None	N
K/H	0.46	ambiguous	0.4523	ambiguous	-0.357	Destabilizing	0.726	D	0.618	neutral	None	None	None	None	N
K/I	0.7913	likely_pathogenic	0.8153	pathogenic	0.384	Stabilizing	0.726	D	0.677	prob.neutral	None	None	None	None	N
K/L	0.7104	likely_pathogenic	0.7136	pathogenic	0.384	Stabilizing	0.272	N	0.54	neutral	None	None	None	None	N
K/M	0.5773	likely_pathogenic	0.6149	pathogenic	0.158	Stabilizing	0.958	D	0.614	neutral	D	0.609759749	None	None	N
K/N	0.5024	ambiguous	0.4936	ambiguous	0.202	Stabilizing	0.497	N	0.547	neutral	D	0.607522446	None	None	N
K/P	0.7355	likely_pathogenic	0.6439	pathogenic	0.295	Stabilizing	0.726	D	0.624	neutral	None	None	None	None	N
K/Q	0.1932	likely_benign	0.2022	benign	0.024	Stabilizing	0.331	N	0.581	neutral	N	0.514443588	None	None	N
K/R	0.0797	likely_benign	0.0749	benign	-0.003	Destabilizing	None	N	0.157	neutral	N	0.50063072	None	None	N
K/S	0.5774	likely_pathogenic	0.5776	pathogenic	-0.28	Destabilizing	0.272	N	0.509	neutral	None	None	None	None	N
K/T	0.3583	ambiguous	0.3988	ambiguous	-0.148	Destabilizing	0.22	N	0.574	neutral	D	0.541227067	None	None	N
K/V	0.7198	likely_pathogenic	0.7429	pathogenic	0.295	Stabilizing	0.567	D	0.574	neutral	None	None	None	None	N
K/W	0.8576	likely_pathogenic	0.8622	pathogenic	-0.278	Destabilizing	0.968	D	0.699	prob.neutral	None	None	None	None	N
K/Y	0.8393	likely_pathogenic	0.8461	pathogenic	0.088	Stabilizing	0.726	D	0.665	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.