TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15527	46804;46805;46806	chr2:178619738;178619737;178619736	chr2:179484465;179484464;179484463
N2AB	13886	41881;41882;41883	chr2:178619738;178619737;178619736	chr2:179484465;179484464;179484463
N2A	12959	39100;39101;39102	chr2:178619738;178619737;178619736	chr2:179484465;179484464;179484463
N2B	6462	19609;19610;19611	chr2:178619738;178619737;178619736	chr2:179484465;179484464;179484463
Novex-1	6587	19984;19985;19986	chr2:178619738;178619737;178619736	chr2:179484465;179484464;179484463
Novex-2	6654	20185;20186;20187	chr2:178619738;178619737;178619736	chr2:179484465;179484464;179484463
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-107
• Domain position: 48
• Structural Position: 123
• Q(SASA): 0.2883
• 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
M/I	rs1310174493	-1.208	0.985	N	0.56	0.35	0.672949579678	gnomAD-2.1.1	9.57E-05	None	None	None	None	N	None	3.4459E-04	0	None	0	0	None	0	None	0	0	0
M/I	rs1310174493	-1.208	0.985	N	0.56	0.35	0.672949579678	gnomAD-3.1.2	1.98E-05	None	None	None	None	N	None	7.25E-05	0	0	0	0	None	0	0	0	0	0
M/I	rs1310174493	-1.208	0.985	N	0.56	0.35	0.672949579678	gnomAD-4.0.0	4.3416E-06	None	None	None	None	N	None	6.68771E-05	0	None	0	0	None	0	0	1.69645E-06	0	0
M/K	rs77496539	-0.925	0.994	D	0.585	0.623	None	gnomAD-2.1.1	1.2084E-04	None	None	None	None	N	None	0	0	None	0	1.5618E-03	None	0	None	0	0	3.32116E-04
M/K	rs77496539	-0.925	0.994	D	0.585	0.623	None	gnomAD-3.1.2	7.91E-05	None	None	None	None	N	None	0	0	0	0	2.33918E-03	None	0	0	0	0	0
M/K	rs77496539	-0.925	0.994	D	0.585	0.623	None	1000 genomes	9.98403E-04	None	None	None	None	N	None	0	0	None	None	5E-03	0	None	None	None	0	None
M/K	rs77496539	-0.925	0.994	D	0.585	0.623	None	gnomAD-4.0.0	1.47602E-04	None	None	None	None	N	None	0	0	None	0	5.13898E-03	None	0	0	8.4823E-07	0	1.12165E-04
M/L	None	None	0.927	N	0.312	0.317	0.651006993216	gnomAD-4.0.0	1.59382E-06	None	None	None	None	N	None	0	0	None	0	2.77685E-05	None	0	0	0	0	0
M/R	None	None	0.998	N	0.588	0.607	0.792895713981	gnomAD-4.0.0	6.84686E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15993E-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
M/A	0.7948	likely_pathogenic	0.8244	pathogenic	-2.355	Highly Destabilizing	0.989	D	0.578	neutral	None	None	None	None	N
M/C	0.8651	likely_pathogenic	0.9011	pathogenic	-1.349	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	N
M/D	0.977	likely_pathogenic	0.9765	pathogenic	-1.12	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
M/E	0.8376	likely_pathogenic	0.8428	pathogenic	-1.067	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
M/F	0.4708	ambiguous	0.5139	ambiguous	-1.243	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	N
M/G	0.9222	likely_pathogenic	0.9316	pathogenic	-2.698	Highly Destabilizing	0.995	D	0.664	neutral	None	None	None	None	N
M/H	0.8206	likely_pathogenic	0.8372	pathogenic	-1.793	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
M/I	0.4962	ambiguous	0.5243	ambiguous	-1.433	Destabilizing	0.985	D	0.56	neutral	N	0.471729863	None	None	N
M/K	0.4275	ambiguous	0.5183	ambiguous	-1.04	Destabilizing	0.994	D	0.585	neutral	D	0.566355013	None	None	N
M/L	0.1813	likely_benign	0.1942	benign	-1.433	Destabilizing	0.927	D	0.312	neutral	N	0.499289699	None	None	N
M/N	0.8523	likely_pathogenic	0.8592	pathogenic	-0.873	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
M/P	0.9622	likely_pathogenic	0.9602	pathogenic	-1.718	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
M/Q	0.5	ambiguous	0.5173	ambiguous	-0.931	Destabilizing	0.999	D	0.522	neutral	None	None	None	None	N
M/R	0.4924	ambiguous	0.5608	ambiguous	-0.566	Destabilizing	0.998	D	0.588	neutral	N	0.50724639	None	None	N
M/S	0.8518	likely_pathogenic	0.8563	pathogenic	-1.491	Destabilizing	0.995	D	0.577	neutral	None	None	None	None	N
M/T	0.6502	likely_pathogenic	0.6306	pathogenic	-1.33	Destabilizing	0.994	D	0.593	neutral	N	0.51336323	None	None	N
M/V	0.1712	likely_benign	0.182	benign	-1.718	Destabilizing	0.985	D	0.434	neutral	N	0.491471961	None	None	N
M/W	0.8	likely_pathogenic	0.8318	pathogenic	-1.173	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
M/Y	0.7606	likely_pathogenic	0.7905	pathogenic	-1.278	Destabilizing	0.999	D	0.604	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.