TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35620	107083;107084;107085	chr2:178528893;178528892;178528891	chr2:179393620;179393619;179393618
N2AB	33979	102160;102161;102162	chr2:178528893;178528892;178528891	chr2:179393620;179393619;179393618
N2A	33052	99379;99380;99381	chr2:178528893;178528892;178528891	chr2:179393620;179393619;179393618
N2B	26555	79888;79889;79890	chr2:178528893;178528892;178528891	chr2:179393620;179393619;179393618
Novex-1	26680	80263;80264;80265	chr2:178528893;178528892;178528891	chr2:179393620;179393619;179393618
Novex-2	26747	80464;80465;80466	chr2:178528893;178528892;178528891	chr2:179393620;179393619;179393618
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-167
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.5579
• 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	rs377593605	-0.035	0.001	N	0.133	0.057	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	2.66E-05	0
E/K	rs377593605	-0.035	0.001	N	0.133	0.057	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	1.20604E-04	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs377593605	-0.035	0.001	N	0.133	0.057	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/K	rs377593605	-0.035	0.001	N	0.133	0.057	None	gnomAD-4.0.0	1.48699E-05	None	None	None	None	N	None	6.66134E-05	0	None	0	2.22777E-05	None	0	0	1.18657E-05	4.39155E-05	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
E/A	0.1402	likely_benign	0.1427	benign	-0.266	Destabilizing	None	N	0.133	neutral	N	0.448341139	None	None	N
E/C	0.8572	likely_pathogenic	0.8677	pathogenic	0.126	Stabilizing	0.676	D	0.369	neutral	None	None	None	None	N
E/D	0.1008	likely_benign	0.0965	benign	-0.222	Destabilizing	None	N	0.096	neutral	N	0.431913036	None	None	N
E/F	0.7577	likely_pathogenic	0.7728	pathogenic	-0.209	Destabilizing	0.356	N	0.393	neutral	None	None	None	None	N
E/G	0.1514	likely_benign	0.1437	benign	-0.451	Destabilizing	0.012	N	0.371	neutral	N	0.450941514	None	None	N
E/H	0.4043	ambiguous	0.4114	ambiguous	0.004	Stabilizing	0.356	N	0.342	neutral	None	None	None	None	N
E/I	0.4142	ambiguous	0.4076	ambiguous	0.182	Stabilizing	0.214	N	0.422	neutral	None	None	None	None	N
E/K	0.11	likely_benign	0.1133	benign	0.499	Stabilizing	0.001	N	0.133	neutral	N	0.449901364	None	None	N
E/L	0.4807	ambiguous	0.4652	ambiguous	0.182	Stabilizing	0.038	N	0.413	neutral	None	None	None	None	N
E/M	0.5386	ambiguous	0.5381	ambiguous	0.293	Stabilizing	0.356	N	0.35	neutral	None	None	None	None	N
E/N	0.2019	likely_benign	0.1989	benign	0.212	Stabilizing	0.038	N	0.24	neutral	None	None	None	None	N
E/P	0.4239	ambiguous	0.4026	ambiguous	0.053	Stabilizing	0.072	N	0.393	neutral	None	None	None	None	N
E/Q	0.1544	likely_benign	0.1544	benign	0.244	Stabilizing	0.006	N	0.245	neutral	N	0.431566319	None	None	N
E/R	0.1965	likely_benign	0.203	benign	0.631	Stabilizing	0.038	N	0.26	neutral	None	None	None	None	N
E/S	0.1583	likely_benign	0.1546	benign	0.053	Stabilizing	0.001	N	0.13	neutral	None	None	None	None	N
E/T	0.2141	likely_benign	0.2135	benign	0.207	Stabilizing	0.038	N	0.321	neutral	None	None	None	None	N
E/V	0.2569	likely_benign	0.2484	benign	0.053	Stabilizing	0.029	N	0.387	neutral	N	0.447994422	None	None	N
E/W	0.8865	likely_pathogenic	0.8884	pathogenic	-0.087	Destabilizing	0.864	D	0.459	neutral	None	None	None	None	N
E/Y	0.588	likely_pathogenic	0.5743	pathogenic	0.038	Stabilizing	0.356	N	0.367	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.