TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2651	8176;8177;8178	chr2:178771376;178771375;178771374	chr2:179636103;179636102;179636101
N2AB	2651	8176;8177;8178	chr2:178771376;178771375;178771374	chr2:179636103;179636102;179636101
N2A	2651	8176;8177;8178	chr2:178771376;178771375;178771374	chr2:179636103;179636102;179636101
N2B	2605	8038;8039;8040	chr2:178771376;178771375;178771374	chr2:179636103;179636102;179636101
Novex-1	2605	8038;8039;8040	chr2:178771376;178771375;178771374	chr2:179636103;179636102;179636101
Novex-2	2605	8038;8039;8040	chr2:178771376;178771375;178771374	chr2:179636103;179636102;179636101
Novex-3	2651	8176;8177;8178	chr2:178771376;178771375;178771374	chr2:179636103;179636102;179636101

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-16
• Domain position: 31
• Structural Position: 47
• Q(SASA): 0.2133
• 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
E/K	rs770388400	-1.176	0.019	N	0.162	0.257	0.314417295294	gnomAD-2.1.1	2.39E-05	None	None	None	None	N	None	1.23031E-04	0	None	0	0	None	9.8E-05	None	0	0	1.63185E-04
E/K	rs770388400	-1.176	0.019	N	0.162	0.257	0.314417295294	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs770388400	-1.176	0.019	N	0.162	0.257	0.314417295294	gnomAD-4.0.0	1.85882E-05	None	None	None	None	N	None	4.00374E-05	0	None	0	2.22906E-05	None	0	1.6442E-04	1.52545E-05	5.48992E-05	3.20092E-05

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
E/A	0.172	likely_benign	0.18	benign	-0.709	Destabilizing	0.425	N	0.44	neutral	N	0.505467566	None	None	N
E/C	0.7791	likely_pathogenic	0.7964	pathogenic	-0.505	Destabilizing	0.995	D	0.564	neutral	None	None	None	None	N
E/D	0.1725	likely_benign	0.1877	benign	-1.17	Destabilizing	0.425	N	0.454	neutral	N	0.501966768	None	None	N
E/F	0.6009	likely_pathogenic	0.6248	pathogenic	0.148	Stabilizing	0.944	D	0.563	neutral	None	None	None	None	N
E/G	0.2261	likely_benign	0.2375	benign	-1.121	Destabilizing	0.425	N	0.519	neutral	N	0.507214285	None	None	N
E/H	0.357	ambiguous	0.3685	ambiguous	-0.106	Destabilizing	0.007	N	0.313	neutral	None	None	None	None	N
E/I	0.2098	likely_benign	0.2204	benign	0.433	Stabilizing	0.944	D	0.585	neutral	None	None	None	None	N
E/K	0.1099	likely_benign	0.1154	benign	-0.802	Destabilizing	0.019	N	0.162	neutral	N	0.411968541	None	None	N
E/L	0.2898	likely_benign	0.297	benign	0.433	Stabilizing	0.704	D	0.555	neutral	None	None	None	None	N
E/M	0.33	likely_benign	0.3452	ambiguous	0.831	Stabilizing	0.944	D	0.529	neutral	None	None	None	None	N
E/N	0.2382	likely_benign	0.2652	benign	-1.358	Destabilizing	0.704	D	0.503	neutral	None	None	None	None	N
E/P	0.936	likely_pathogenic	0.9141	pathogenic	0.074	Stabilizing	0.828	D	0.521	neutral	None	None	None	None	N
E/Q	0.1106	likely_benign	0.1152	benign	-1.154	Destabilizing	0.025	N	0.159	neutral	N	0.435068397	None	None	N
E/R	0.2025	likely_benign	0.2057	benign	-0.42	Destabilizing	0.007	N	0.161	neutral	None	None	None	None	N
E/S	0.1992	likely_benign	0.2155	benign	-1.704	Destabilizing	0.495	N	0.468	neutral	None	None	None	None	N
E/T	0.1768	likely_benign	0.1948	benign	-1.357	Destabilizing	0.704	D	0.545	neutral	None	None	None	None	N
E/V	0.1484	likely_benign	0.1534	benign	0.074	Stabilizing	0.784	D	0.547	neutral	N	0.496805697	None	None	N
E/W	0.8247	likely_pathogenic	0.8353	pathogenic	0.406	Stabilizing	0.995	D	0.579	neutral	None	None	None	None	N
E/Y	0.4973	ambiguous	0.5132	ambiguous	0.392	Stabilizing	0.893	D	0.55	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.