TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31878	95857;95858;95859	chr2:178545478;178545477;178545476	chr2:179410205;179410204;179410203
N2AB	30237	90934;90935;90936	chr2:178545478;178545477;178545476	chr2:179410205;179410204;179410203
N2A	29310	88153;88154;88155	chr2:178545478;178545477;178545476	chr2:179410205;179410204;179410203
N2B	22813	68662;68663;68664	chr2:178545478;178545477;178545476	chr2:179410205;179410204;179410203
Novex-1	22938	69037;69038;69039	chr2:178545478;178545477;178545476	chr2:179410205;179410204;179410203
Novex-2	23005	69238;69239;69240	chr2:178545478;178545477;178545476	chr2:179410205;179410204;179410203
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-120
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.1608
• 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
D/N	rs752844593	-1.201	0.001	N	0.311	0.086	0.151104730317	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
D/N	rs752844593	-1.201	0.001	N	0.311	0.086	0.151104730317	gnomAD-4.0.0	3.62726E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.76846E-05	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
D/A	0.189	likely_benign	0.1861	benign	-0.5	Destabilizing	0.001	N	0.371	neutral	N	0.436999143	None	None	N
D/C	0.5228	ambiguous	0.5404	ambiguous	-0.063	Destabilizing	0.944	D	0.636	neutral	None	None	None	None	N
D/E	0.1299	likely_benign	0.1402	benign	-0.346	Destabilizing	0.001	N	0.151	neutral	N	0.302394288	None	None	N
D/F	0.5039	ambiguous	0.5137	ambiguous	0.222	Stabilizing	0.818	D	0.655	neutral	None	None	None	None	N
D/G	0.2755	likely_benign	0.2834	benign	-0.922	Destabilizing	0.09	N	0.438	neutral	N	0.45799049	None	None	N
D/H	0.247	likely_benign	0.2501	benign	-0.033	Destabilizing	0.627	D	0.583	neutral	N	0.49533537	None	None	N
D/I	0.2737	likely_benign	0.2825	benign	0.647	Stabilizing	0.69	D	0.631	neutral	None	None	None	None	N
D/K	0.4016	ambiguous	0.4329	ambiguous	-0.168	Destabilizing	0.241	N	0.469	neutral	None	None	None	None	N
D/L	0.2994	likely_benign	0.3211	benign	0.647	Stabilizing	0.241	N	0.572	neutral	None	None	None	None	N
D/M	0.4881	ambiguous	0.5162	ambiguous	1.151	Stabilizing	0.944	D	0.629	neutral	None	None	None	None	N
D/N	0.0995	likely_benign	0.1078	benign	-0.76	Destabilizing	0.001	N	0.311	neutral	N	0.437844505	None	None	N
D/P	0.7313	likely_pathogenic	0.7293	pathogenic	0.29	Stabilizing	0.818	D	0.555	neutral	None	None	None	None	N
D/Q	0.2743	likely_benign	0.2889	benign	-0.545	Destabilizing	0.008	N	0.309	neutral	None	None	None	None	N
D/R	0.4335	ambiguous	0.4438	ambiguous	-0.004	Destabilizing	0.241	N	0.549	neutral	None	None	None	None	N
D/S	0.1146	likely_benign	0.1169	benign	-1.144	Destabilizing	0.116	N	0.428	neutral	None	None	None	None	N
D/T	0.1986	likely_benign	0.2078	benign	-0.771	Destabilizing	0.388	N	0.485	neutral	None	None	None	None	N
D/V	0.1877	likely_benign	0.1913	benign	0.29	Stabilizing	0.193	N	0.58	neutral	N	0.441194241	None	None	N
D/W	0.842	likely_pathogenic	0.8502	pathogenic	0.478	Stabilizing	0.981	D	0.666	neutral	None	None	None	None	N
D/Y	0.2124	likely_benign	0.2186	benign	0.526	Stabilizing	0.912	D	0.668	neutral	N	0.436596498	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.