TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1877	5854;5855;5856	chr2:178776235;178776234;178776233	chr2:179640962;179640961;179640960
N2AB	1877	5854;5855;5856	chr2:178776235;178776234;178776233	chr2:179640962;179640961;179640960
N2A	1877	5854;5855;5856	chr2:178776235;178776234;178776233	chr2:179640962;179640961;179640960
N2B	1831	5716;5717;5718	chr2:178776235;178776234;178776233	chr2:179640962;179640961;179640960
Novex-1	1831	5716;5717;5718	chr2:178776235;178776234;178776233	chr2:179640962;179640961;179640960
Novex-2	1831	5716;5717;5718	chr2:178776235;178776234;178776233	chr2:179640962;179640961;179640960
Novex-3	1877	5854;5855;5856	chr2:178776235;178776234;178776233	chr2:179640962;179640961;179640960

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-9
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.9792
• 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
N/I	rs1554006798	None	1.0	D	0.679	0.517	0.571828761226	gnomAD-4.0.0	6.36207E-06	None	None	None	None	N	None	0	0	None	0	1.10902E-04	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
N/A	0.8955	likely_pathogenic	0.9095	pathogenic	-0.447	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
N/C	0.8604	likely_pathogenic	0.8734	pathogenic	0.356	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
N/D	0.746	likely_pathogenic	0.7268	pathogenic	-0.008	Destabilizing	0.999	D	0.642	neutral	N	0.419714987	None	None	N
N/E	0.974	likely_pathogenic	0.9748	pathogenic	-0.035	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
N/F	0.9868	likely_pathogenic	0.9897	pathogenic	-0.753	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
N/G	0.6574	likely_pathogenic	0.666	pathogenic	-0.638	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	N
N/H	0.6728	likely_pathogenic	0.689	pathogenic	-0.711	Destabilizing	1.0	D	0.621	neutral	D	0.549815624	None	None	N
N/I	0.9861	likely_pathogenic	0.9887	pathogenic	-0.026	Destabilizing	1.0	D	0.679	prob.neutral	D	0.648500453	None	None	N
N/K	0.9741	likely_pathogenic	0.9752	pathogenic	0.097	Stabilizing	1.0	D	0.651	neutral	N	0.459480131	None	None	N
N/L	0.9216	likely_pathogenic	0.9346	pathogenic	-0.026	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
N/M	0.9641	likely_pathogenic	0.971	pathogenic	0.459	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
N/P	0.9896	likely_pathogenic	0.9918	pathogenic	-0.139	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
N/Q	0.9151	likely_pathogenic	0.9225	pathogenic	-0.415	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
N/R	0.9516	likely_pathogenic	0.954	pathogenic	0.147	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
N/S	0.2889	likely_benign	0.2963	benign	-0.166	Destabilizing	0.999	D	0.61	neutral	N	0.473069506	None	None	N
N/T	0.8934	likely_pathogenic	0.9054	pathogenic	-0.045	Destabilizing	0.999	D	0.651	neutral	D	0.608156324	None	None	N
N/V	0.9763	likely_pathogenic	0.9808	pathogenic	-0.139	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
N/W	0.9936	likely_pathogenic	0.995	pathogenic	-0.672	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
N/Y	0.8812	likely_pathogenic	0.8988	pathogenic	-0.424	Destabilizing	1.0	D	0.647	neutral	D	0.610240681	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.