TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26628	80107;80108;80109	chr2:178566250;178566249;178566248	chr2:179430977;179430976;179430975
N2AB	24987	75184;75185;75186	chr2:178566250;178566249;178566248	chr2:179430977;179430976;179430975
N2A	24060	72403;72404;72405	chr2:178566250;178566249;178566248	chr2:179430977;179430976;179430975
N2B	17563	52912;52913;52914	chr2:178566250;178566249;178566248	chr2:179430977;179430976;179430975
Novex-1	17688	53287;53288;53289	chr2:178566250;178566249;178566248	chr2:179430977;179430976;179430975
Novex-2	17755	53488;53489;53490	chr2:178566250;178566249;178566248	chr2:179430977;179430976;179430975
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGA
• RefSeq wild type template codon: GCT
• Domain: Ig-138
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.312
• 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
R/L	rs201091376	-0.57	0.251	N	0.509	0.158	0.327686398923	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	6.46E-05	2.9E-05	None	0	0	None	0	None	0	0	0
R/L	rs201091376	-0.57	0.251	N	0.509	0.158	0.327686398923	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
R/L	rs201091376	-0.57	0.251	N	0.509	0.158	0.327686398923	gnomAD-4.0.0	1.85925E-06	None	None	None	None	N	None	2.67058E-05	1.66728E-05	None	0	0	None	0	0	0	0	0
R/P	rs201091376	-1.244	0.705	N	0.583	0.322	None	gnomAD-2.1.1	5.71E-05	None	None	None	None	N	None	5.78752E-04	5.66E-05	None	0	0	None	0	None	0	0	0
R/P	rs201091376	-1.244	0.705	N	0.583	0.322	None	gnomAD-3.1.2	1.51206E-04	None	None	None	None	N	None	5.30991E-04	6.55E-05	0	0	0	None	0	0	0	0	0
R/P	rs201091376	-1.244	0.705	N	0.583	0.322	None	gnomAD-4.0.0	2.91282E-05	None	None	None	None	N	None	5.60823E-04	5.00183E-05	None	0	0	None	0	0	0	0	3.20266E-05
R/Q	None	-0.701	0.271	N	0.524	0.17	0.0954503805726	gnomAD-2.1.1	2.97392E-04	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	2.32011E-03	None	0	1.78E-05	0
R/Q	None	-0.701	0.271	N	0.524	0.17	0.0954503805726	gnomAD-3.1.2	1.05187E-04	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	3.1043E-03	0
R/Q	None	-0.701	0.271	N	0.524	0.17	0.0954503805726	1000 genomes	7.98722E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	4.1E-03	None
R/Q	None	-0.701	0.271	N	0.524	0.17	0.0954503805726	gnomAD-4.0.0	1.38194E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.61059E-05	2.19597E-03	6.40307E-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
R/A	0.7231	likely_pathogenic	0.7491	pathogenic	-1.88	Destabilizing	0.035	N	0.495	neutral	None	None	None	None	N
R/C	0.3411	ambiguous	0.3344	benign	-1.763	Destabilizing	0.935	D	0.616	neutral	None	None	None	None	N
R/D	0.9294	likely_pathogenic	0.9346	pathogenic	-0.311	Destabilizing	0.149	N	0.559	neutral	None	None	None	None	N
R/E	0.6689	likely_pathogenic	0.6859	pathogenic	-0.117	Destabilizing	0.035	N	0.516	neutral	None	None	None	None	N
R/F	0.7484	likely_pathogenic	0.7564	pathogenic	-1.4	Destabilizing	0.791	D	0.607	neutral	None	None	None	None	N
R/G	0.5934	likely_pathogenic	0.616	pathogenic	-2.224	Highly Destabilizing	0.251	N	0.509	neutral	N	0.464089586	None	None	N
R/H	0.2273	likely_benign	0.2221	benign	-2.078	Highly Destabilizing	0.555	D	0.513	neutral	None	None	None	None	N
R/I	0.5086	ambiguous	0.5046	ambiguous	-0.901	Destabilizing	0.555	D	0.593	neutral	None	None	None	None	N
R/K	0.0872	likely_benign	0.1058	benign	-1.167	Destabilizing	None	N	0.143	neutral	None	None	None	None	N
R/L	0.4127	ambiguous	0.4469	ambiguous	-0.901	Destabilizing	0.251	N	0.509	neutral	N	0.493612069	None	None	N
R/M	0.4311	ambiguous	0.4784	ambiguous	-1.277	Destabilizing	0.791	D	0.569	neutral	None	None	None	None	N
R/N	0.8681	likely_pathogenic	0.8806	pathogenic	-0.942	Destabilizing	0.149	N	0.497	neutral	None	None	None	None	N
R/P	0.8968	likely_pathogenic	0.9107	pathogenic	-1.213	Destabilizing	0.705	D	0.583	neutral	N	0.475863965	None	None	N
R/Q	0.1849	likely_benign	0.1909	benign	-1.015	Destabilizing	0.271	N	0.524	neutral	N	0.463582607	None	None	N
R/S	0.8375	likely_pathogenic	0.8473	pathogenic	-2.058	Highly Destabilizing	0.081	N	0.491	neutral	None	None	None	None	N
R/T	0.6071	likely_pathogenic	0.621	pathogenic	-1.64	Destabilizing	0.149	N	0.507	neutral	None	None	None	None	N
R/V	0.5865	likely_pathogenic	0.602	pathogenic	-1.213	Destabilizing	0.38	N	0.577	neutral	None	None	None	None	N
R/W	0.358	ambiguous	0.3682	ambiguous	-0.809	Destabilizing	0.935	D	0.637	neutral	None	None	None	None	N
R/Y	0.6607	likely_pathogenic	0.6654	pathogenic	-0.664	Destabilizing	0.791	D	0.583	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.