TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9990	30193;30194;30195	chr2:178704402;178704401;178704400	chr2:179569129;179569128;179569127
N2AB	9673	29242;29243;29244	chr2:178704402;178704401;178704400	chr2:179569129;179569128;179569127
N2A	8746	26461;26462;26463	chr2:178704402;178704401;178704400	chr2:179569129;179569128;179569127
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-85
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.2468
• 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
A/V	rs1447594243	0.81	0.001	None	0.149	0.086	0.144782658237	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
A/V	rs1447594243	0.81	0.001	None	0.149	0.086	0.144782658237	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
A/V	rs1447594243	0.81	0.001	None	0.149	0.086	0.144782658237	gnomAD-4.0.0	6.56909E-06	None	None	None	None	N	None	2.41208E-05	0	None	0	0	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
A/C	0.6853	likely_pathogenic	0.728	pathogenic	-0.715	Destabilizing	0.944	D	0.435	neutral	None	None	None	None	N
A/D	0.4501	ambiguous	0.4899	ambiguous	-0.752	Destabilizing	0.388	N	0.424	neutral	None	None	None	None	N
A/E	0.2807	likely_benign	0.3131	benign	-0.729	Destabilizing	0.324	N	0.386	neutral	None	None	None	None	N
A/F	0.449	ambiguous	0.5039	ambiguous	-0.761	Destabilizing	0.69	D	0.458	neutral	None	None	None	None	N
A/G	0.2269	likely_benign	0.2555	benign	-0.981	Destabilizing	0.165	N	0.427	neutral	None	None	None	None	N
A/H	0.5526	ambiguous	0.6037	pathogenic	-0.885	Destabilizing	0.981	D	0.443	neutral	None	None	None	None	N
A/I	0.3006	likely_benign	0.3676	ambiguous	-0.123	Destabilizing	0.116	N	0.458	neutral	None	None	None	None	N
A/K	0.433	ambiguous	0.4632	ambiguous	-0.804	Destabilizing	0.241	N	0.438	neutral	None	None	None	None	N
A/L	0.2571	likely_benign	0.3174	benign	-0.123	Destabilizing	0.116	N	0.45	neutral	None	None	None	None	N
A/M	0.2999	likely_benign	0.3654	ambiguous	-0.337	Destabilizing	0.818	D	0.419	neutral	None	None	None	None	N
A/N	0.3332	likely_benign	0.3856	ambiguous	-0.677	Destabilizing	0.69	D	0.424	neutral	None	None	None	None	N
A/P	0.8784	likely_pathogenic	0.9225	pathogenic	-0.28	Destabilizing	0.773	D	0.387	neutral	None	None	None	None	N
A/Q	0.3193	likely_benign	0.3574	ambiguous	-0.727	Destabilizing	0.69	D	0.403	neutral	None	None	None	None	N
A/R	0.3585	ambiguous	0.3574	ambiguous	-0.57	Destabilizing	0.002	N	0.321	neutral	None	None	None	None	N
A/S	0.1016	likely_benign	0.1078	benign	-1.055	Destabilizing	0.09	N	0.469	neutral	None	None	None	None	N
A/T	0.0891	likely_benign	0.1022	benign	-0.913	Destabilizing	0.001	N	0.163	neutral	None	None	None	None	N
A/V	0.145	likely_benign	0.1786	benign	-0.28	Destabilizing	0.001	N	0.149	neutral	None	None	None	None	N
A/W	0.8955	likely_pathogenic	0.9153	pathogenic	-1.09	Destabilizing	0.981	D	0.5	neutral	None	None	None	None	N
A/Y	0.6556	likely_pathogenic	0.7039	pathogenic	-0.64	Destabilizing	0.818	D	0.465	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.