TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2570	7933;7934;7935	chr2:178773256;178773255;178773254	chr2:179637983;179637982;179637981
N2AB	2570	7933;7934;7935	chr2:178773256;178773255;178773254	chr2:179637983;179637982;179637981
N2A	2570	7933;7934;7935	chr2:178773256;178773255;178773254	chr2:179637983;179637982;179637981
N2B	2524	7795;7796;7797	chr2:178773256;178773255;178773254	chr2:179637983;179637982;179637981
Novex-1	2524	7795;7796;7797	chr2:178773256;178773255;178773254	chr2:179637983;179637982;179637981
Novex-2	2524	7795;7796;7797	chr2:178773256;178773255;178773254	chr2:179637983;179637982;179637981
Novex-3	2570	7933;7934;7935	chr2:178773256;178773255;178773254	chr2:179637983;179637982;179637981

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-15
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.5513
• 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
K/E	rs779361884	0.43	None	N	0.151	0.239	0.256793551483	gnomAD-2.1.1	2E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.63409E-04	None	0	0	0
K/E	rs779361884	0.43	None	N	0.151	0.239	0.256793551483	gnomAD-4.0.0	6.84154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.04345E-04	1.65612E-05
K/M	None	None	0.171	N	0.273	0.293	0.37479162749	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
K/Q	rs779361884	None	None	N	0.119	0.136	0.212008924253	gnomAD-4.0.0	6.84154E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99339E-07	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
K/A	0.2514	likely_benign	0.2282	benign	-0.043	Destabilizing	0.031	N	0.305	neutral	None	None	None	None	N
K/C	0.5846	likely_pathogenic	0.5801	pathogenic	-0.211	Destabilizing	0.864	D	0.255	neutral	None	None	None	None	N
K/D	0.3482	ambiguous	0.3085	benign	-0.01	Destabilizing	0.016	N	0.352	neutral	None	None	None	None	N
K/E	0.0971	likely_benign	0.0885	benign	0.02	Stabilizing	None	N	0.151	neutral	N	0.426093536	None	None	N
K/F	0.6956	likely_pathogenic	0.6857	pathogenic	-0.141	Destabilizing	0.214	N	0.301	neutral	None	None	None	None	N
K/G	0.3506	ambiguous	0.3222	benign	-0.282	Destabilizing	0.016	N	0.333	neutral	None	None	None	None	N
K/H	0.2678	likely_benign	0.2614	benign	-0.594	Destabilizing	0.214	N	0.273	neutral	None	None	None	None	N
K/I	0.2627	likely_benign	0.2449	benign	0.517	Stabilizing	0.038	N	0.396	neutral	None	None	None	None	N
K/L	0.2919	likely_benign	0.2795	benign	0.517	Stabilizing	None	N	0.199	neutral	None	None	None	None	N
K/M	0.1805	likely_benign	0.1741	benign	0.242	Stabilizing	0.171	N	0.273	neutral	N	0.513978802	None	None	N
K/N	0.2228	likely_benign	0.1981	benign	0.082	Stabilizing	None	N	0.141	neutral	N	0.511549245	None	None	N
K/P	0.8992	likely_pathogenic	0.8671	pathogenic	0.359	Stabilizing	0.136	N	0.373	neutral	None	None	None	None	N
K/Q	0.0967	likely_benign	0.0953	benign	-0.038	Destabilizing	None	N	0.119	neutral	N	0.387402184	None	None	N
K/R	0.0927	likely_benign	0.0929	benign	-0.185	Destabilizing	0.012	N	0.256	neutral	N	0.496403082	None	None	N
K/S	0.2539	likely_benign	0.2313	benign	-0.38	Destabilizing	0.016	N	0.213	neutral	None	None	None	None	N
K/T	0.1158	likely_benign	0.1047	benign	-0.189	Destabilizing	0.012	N	0.337	neutral	N	0.496768553	None	None	N
K/V	0.2417	likely_benign	0.2181	benign	0.359	Stabilizing	0.016	N	0.357	neutral	None	None	None	None	N
K/W	0.7357	likely_pathogenic	0.744	pathogenic	-0.162	Destabilizing	0.864	D	0.259	neutral	None	None	None	None	N
K/Y	0.5564	ambiguous	0.5439	ambiguous	0.175	Stabilizing	0.628	D	0.317	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.