TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18724	56395;56396;56397	chr2:178599731;178599730;178599729	chr2:179464458;179464457;179464456
N2AB	17083	51472;51473;51474	chr2:178599731;178599730;178599729	chr2:179464458;179464457;179464456
N2A	16156	48691;48692;48693	chr2:178599731;178599730;178599729	chr2:179464458;179464457;179464456
N2B	9659	29200;29201;29202	chr2:178599731;178599730;178599729	chr2:179464458;179464457;179464456
Novex-1	9784	29575;29576;29577	chr2:178599731;178599730;178599729	chr2:179464458;179464457;179464456
Novex-2	9851	29776;29777;29778	chr2:178599731;178599730;178599729	chr2:179464458;179464457;179464456
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-116
• Domain position: 37
• Structural Position: 56
• Q(SASA): 0.7548
• 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	rs1559671221	None	0.012	N	0.329	0.173	0.243972157842	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
K/E	rs1559671221	None	0.012	N	0.329	0.173	0.243972157842	gnomAD-4.0.0	2.7383E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5993E-06	0	0
K/R	rs201091423	0.182	None	N	0.231	0.087	None	gnomAD-2.1.1	5.37E-05	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	0	None	0	1.0973E-04	0
K/R	rs201091423	0.182	None	N	0.231	0.087	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.17689E-04	0	0
K/R	rs201091423	0.182	None	N	0.231	0.087	None	gnomAD-4.0.0	4.21579E-05	None	None	None	None	N	None	2.66702E-05	1.66806E-05	None	0	0	None	1.56235E-05	0	5.42682E-05	0	0
K/T	rs201091423	0.051	0.055	N	0.329	0.135	0.256283259241	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	1.2945E-04	0	None	0	0	None	0	None	0	2.67E-05	0
K/T	rs201091423	0.051	0.055	N	0.329	0.135	0.256283259241	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs201091423	0.051	0.055	N	0.329	0.135	0.256283259241	gnomAD-4.0.0	1.79804E-05	None	None	None	None	N	None	2.67137E-05	0	None	0	0	None	0	0	2.20463E-05	0	1.6019E-05

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	0.2014	likely_benign	0.1759	benign	0.077	Stabilizing	None	N	0.117	neutral	None	None	None	None	N
K/C	0.5204	ambiguous	0.4876	ambiguous	-0.365	Destabilizing	0.864	D	0.355	neutral	None	None	None	None	N
K/D	0.3068	likely_benign	0.2811	benign	-0.324	Destabilizing	None	N	0.205	neutral	None	None	None	None	N
K/E	0.1128	likely_benign	0.1111	benign	-0.321	Destabilizing	0.012	N	0.329	neutral	N	0.399433337	None	None	N
K/F	0.5647	likely_pathogenic	0.4984	ambiguous	-0.23	Destabilizing	0.356	N	0.36	neutral	None	None	None	None	N
K/G	0.2153	likely_benign	0.1887	benign	-0.066	Destabilizing	None	N	0.16	neutral	None	None	None	None	N
K/H	0.2257	likely_benign	0.1993	benign	-0.173	Destabilizing	0.356	N	0.35	neutral	None	None	None	None	N
K/I	0.2712	likely_benign	0.2363	benign	0.377	Stabilizing	0.356	N	0.397	neutral	None	None	None	None	N
K/L	0.2383	likely_benign	0.1947	benign	0.377	Stabilizing	0.072	N	0.355	neutral	None	None	None	None	N
K/M	0.2028	likely_benign	0.1649	benign	-0.137	Destabilizing	0.56	D	0.35	neutral	N	0.441669536	None	None	N
K/N	0.2364	likely_benign	0.2062	benign	0.079	Stabilizing	0.055	N	0.301	neutral	N	0.467063839	None	None	N
K/P	0.3663	ambiguous	0.3695	ambiguous	0.301	Stabilizing	0.136	N	0.385	neutral	None	None	None	None	N
K/Q	0.0986	likely_benign	0.0906	benign	-0.024	Destabilizing	0.001	N	0.214	neutral	N	0.440629386	None	None	N
K/R	0.0745	likely_benign	0.0712	benign	-0.033	Destabilizing	None	N	0.231	neutral	N	0.453193251	None	None	N
K/S	0.2266	likely_benign	0.1931	benign	-0.223	Destabilizing	0.016	N	0.301	neutral	None	None	None	None	N
K/T	0.145	likely_benign	0.1284	benign	-0.102	Destabilizing	0.055	N	0.329	neutral	N	0.475992753	None	None	N
K/V	0.2225	likely_benign	0.1912	benign	0.301	Stabilizing	0.072	N	0.378	neutral	None	None	None	None	N
K/W	0.6025	likely_pathogenic	0.5261	ambiguous	-0.372	Destabilizing	0.864	D	0.382	neutral	None	None	None	None	N
K/Y	0.445	ambiguous	0.3952	ambiguous	-0.016	Destabilizing	0.356	N	0.362	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.