TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20336	61231;61232;61233	chr2:178590719;178590718;178590717	chr2:179455446;179455445;179455444
N2AB	18695	56308;56309;56310	chr2:178590719;178590718;178590717	chr2:179455446;179455445;179455444
N2A	17768	53527;53528;53529	chr2:178590719;178590718;178590717	chr2:179455446;179455445;179455444
N2B	11271	34036;34037;34038	chr2:178590719;178590718;178590717	chr2:179455446;179455445;179455444
Novex-1	11396	34411;34412;34413	chr2:178590719;178590718;178590717	chr2:179455446;179455445;179455444
Novex-2	11463	34612;34613;34614	chr2:178590719;178590718;178590717	chr2:179455446;179455445;179455444
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-35
• Domain position: 66
• Structural Position: 98
• Q(SASA): 0.6727
• 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
Y/C	rs1471127612	0.09	0.999	N	0.609	0.323	0.410469974859	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	3.44828E-03	0	None	0	None	0	0	0
Y/C	rs1471127612	0.09	0.999	N	0.609	0.323	0.410469974859	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	2.88184E-04	0	None	0	0	0	0	0
Y/C	rs1471127612	0.09	0.999	N	0.609	0.323	0.410469974859	gnomAD-4.0.0	6.57488E-06	None	None	None	None	N	None	0	0	None	2.88184E-04	0	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
Y/A	0.4469	ambiguous	0.4347	ambiguous	-1.032	Destabilizing	0.959	D	0.557	neutral	None	None	None	None	N
Y/C	0.1202	likely_benign	0.1315	benign	-0.186	Destabilizing	0.999	D	0.609	neutral	N	0.442290319	None	None	N
Y/D	0.3891	ambiguous	0.4083	ambiguous	0.699	Stabilizing	0.995	D	0.615	neutral	N	0.364752255	None	None	N
Y/E	0.6235	likely_pathogenic	0.6279	pathogenic	0.719	Stabilizing	0.996	D	0.604	neutral	None	None	None	None	N
Y/F	0.0782	likely_benign	0.071	benign	-0.41	Destabilizing	0.011	N	0.191	neutral	N	0.350534951	None	None	N
Y/G	0.42	ambiguous	0.4152	ambiguous	-1.258	Destabilizing	0.988	D	0.517	neutral	None	None	None	None	N
Y/H	0.1672	likely_benign	0.1866	benign	0.026	Stabilizing	0.995	D	0.569	neutral	N	0.396517957	None	None	N
Y/I	0.3695	ambiguous	0.3545	ambiguous	-0.422	Destabilizing	0.851	D	0.599	neutral	None	None	None	None	N
Y/K	0.5878	likely_pathogenic	0.5847	pathogenic	-0.124	Destabilizing	0.996	D	0.605	neutral	None	None	None	None	N
Y/L	0.3441	ambiguous	0.3413	ambiguous	-0.422	Destabilizing	0.702	D	0.567	neutral	None	None	None	None	N
Y/M	0.4682	ambiguous	0.447	ambiguous	-0.353	Destabilizing	0.988	D	0.598	neutral	None	None	None	None	N
Y/N	0.1957	likely_benign	0.2081	benign	-0.398	Destabilizing	0.995	D	0.609	neutral	N	0.374814533	None	None	N
Y/P	0.8049	likely_pathogenic	0.769	pathogenic	-0.609	Destabilizing	0.996	D	0.617	neutral	None	None	None	None	N
Y/Q	0.4073	ambiguous	0.4289	ambiguous	-0.296	Destabilizing	0.996	D	0.594	neutral	None	None	None	None	N
Y/R	0.4032	ambiguous	0.4003	ambiguous	0.129	Stabilizing	0.996	D	0.601	neutral	None	None	None	None	N
Y/S	0.1907	likely_benign	0.1892	benign	-0.874	Destabilizing	0.984	D	0.525	neutral	N	0.336757577	None	None	N
Y/T	0.3274	likely_benign	0.3312	benign	-0.759	Destabilizing	0.988	D	0.541	neutral	None	None	None	None	N
Y/V	0.2943	likely_benign	0.2833	benign	-0.609	Destabilizing	0.919	D	0.578	neutral	None	None	None	None	N
Y/W	0.3639	ambiguous	0.3781	ambiguous	-0.377	Destabilizing	0.996	D	0.567	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.