TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14309	43150;43151;43152	chr2:178633434;178633433;178633432	chr2:179498161;179498160;179498159
N2AB	12668	38227;38228;38229	chr2:178633434;178633433;178633432	chr2:179498161;179498160;179498159
N2A	11741	35446;35447;35448	chr2:178633434;178633433;178633432	chr2:179498161;179498160;179498159
N2B	5244	15955;15956;15957	chr2:178633434;178633433;178633432	chr2:179498161;179498160;179498159
Novex-1	5369	16330;16331;16332	chr2:178633434;178633433;178633432	chr2:179498161;179498160;179498159
Novex-2	5436	16531;16532;16533	chr2:178633434;178633433;178633432	chr2:179498161;179498160;179498159
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-93
• Domain position: 79
• Structural Position: 171
• Q(SASA): 0.5944
• 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	rs908530219	0.431	0.101	N	0.515	0.108	0.229924730088	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/E	rs908530219	0.431	0.101	N	0.515	0.108	0.229924730088	gnomAD-4.0.0	7.9614E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.42989E-05	0	0
K/R	None	None	0.213	N	0.496	0.095	0.274366138417	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	1.94099E-04	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
K/A	0.1554	likely_benign	0.1625	benign	-0.325	Destabilizing	0.129	N	0.448	neutral	None	None	None	None	N
K/C	0.59	likely_pathogenic	0.555	ambiguous	-0.412	Destabilizing	0.983	D	0.529	neutral	None	None	None	None	N
K/D	0.4418	ambiguous	0.4242	ambiguous	0.043	Stabilizing	0.129	N	0.511	neutral	None	None	None	None	N
K/E	0.1122	likely_benign	0.1148	benign	0.108	Stabilizing	0.101	N	0.515	neutral	N	0.46800203	None	None	N
K/F	0.5662	likely_pathogenic	0.5246	ambiguous	-0.184	Destabilizing	0.836	D	0.536	neutral	None	None	None	None	N
K/G	0.3379	likely_benign	0.3122	benign	-0.636	Destabilizing	0.129	N	0.496	neutral	None	None	None	None	N
K/H	0.2288	likely_benign	0.2333	benign	-0.968	Destabilizing	0.716	D	0.553	neutral	None	None	None	None	N
K/I	0.1599	likely_benign	0.1611	benign	0.449	Stabilizing	0.716	D	0.575	neutral	None	None	None	None	N
K/L	0.2135	likely_benign	0.2107	benign	0.449	Stabilizing	0.264	N	0.531	neutral	None	None	None	None	N
K/M	0.1214	likely_benign	0.1238	benign	0.283	Stabilizing	0.794	D	0.552	neutral	N	0.508646526	None	None	N
K/N	0.2343	likely_benign	0.2265	benign	-0.171	Destabilizing	0.001	N	0.245	neutral	N	0.493966388	None	None	N
K/P	0.7831	likely_pathogenic	0.7599	pathogenic	0.222	Stabilizing	0.593	D	0.579	neutral	None	None	None	None	N
K/Q	0.1053	likely_benign	0.1129	benign	-0.304	Destabilizing	0.007	N	0.301	neutral	N	0.503632552	None	None	N
K/R	0.0894	likely_benign	0.0873	benign	-0.421	Destabilizing	0.213	N	0.496	neutral	N	0.513213673	None	None	N
K/S	0.1871	likely_benign	0.1867	benign	-0.782	Destabilizing	0.004	N	0.253	neutral	None	None	None	None	N
K/T	0.0672	likely_benign	0.071	benign	-0.532	Destabilizing	0.003	N	0.336	neutral	N	0.42605405	None	None	N
K/V	0.1378	likely_benign	0.1479	benign	0.222	Stabilizing	0.264	N	0.547	neutral	None	None	None	None	N
K/W	0.7208	likely_pathogenic	0.6852	pathogenic	-0.084	Destabilizing	0.983	D	0.554	neutral	None	None	None	None	N
K/Y	0.4884	ambiguous	0.4507	ambiguous	0.216	Stabilizing	0.836	D	0.533	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.