TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34960	105103;105104;105105	chr2:178531737;178531736;178531735	chr2:179396464;179396463;179396462
N2AB	33319	100180;100181;100182	chr2:178531737;178531736;178531735	chr2:179396464;179396463;179396462
N2A	32392	97399;97400;97401	chr2:178531737;178531736;178531735	chr2:179396464;179396463;179396462
N2B	25895	77908;77909;77910	chr2:178531737;178531736;178531735	chr2:179396464;179396463;179396462
Novex-1	26020	78283;78284;78285	chr2:178531737;178531736;178531735	chr2:179396464;179396463;179396462
Novex-2	26087	78484;78485;78486	chr2:178531737;178531736;178531735	chr2:179396464;179396463;179396462
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Ig-163
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2584
• 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
R/C	rs772702110	-0.396	0.005	N	0.477	0.061	0.247872288689	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	5.79E-05	None	0	0	None	3.27E-05	None	0	2.66E-05	0
R/C	rs772702110	-0.396	0.005	N	0.477	0.061	0.247872288689	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.30907E-04	0	0	0	None	0	0	0	0	0
R/C	rs772702110	-0.396	0.005	N	0.477	0.061	0.247872288689	gnomAD-4.0.0	2.16881E-05	None	None	None	None	N	None	0	6.66689E-05	None	0	0	None	0	0	2.45791E-05	2.19582E-05	0
R/H	rs1352552140	None	0.005	N	0.428	0.085	0.0920862733494	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs1352552140	None	0.005	N	0.428	0.085	0.0920862733494	gnomAD-4.0.0	3.0983E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.56255E-05	0	3.39023E-06	0	0
R/P	rs1352552140	None	0.705	N	0.561	0.251	0.303781844768	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/P	rs1352552140	None	0.705	N	0.561	0.251	0.303781844768	gnomAD-4.0.0	6.57471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47037E-05	0	0
R/S	rs772702110	None	0.251	N	0.505	0.104	0.0954503805726	gnomAD-4.0.0	6.84141E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99399E-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
R/A	0.5365	ambiguous	0.8709	pathogenic	-0.536	Destabilizing	0.035	N	0.517	neutral	None	None	None	None	N
R/C	0.128	likely_benign	0.3693	ambiguous	-0.509	Destabilizing	0.005	N	0.477	neutral	N	0.50034604	None	None	N
R/D	0.83	likely_pathogenic	0.9675	pathogenic	0.008	Stabilizing	0.38	N	0.551	neutral	None	None	None	None	N
R/E	0.6024	likely_pathogenic	0.8741	pathogenic	0.124	Stabilizing	0.081	N	0.552	neutral	None	None	None	None	N
R/F	0.6468	likely_pathogenic	0.9292	pathogenic	-0.425	Destabilizing	0.38	N	0.568	neutral	None	None	None	None	N
R/G	0.4696	ambiguous	0.8361	pathogenic	-0.832	Destabilizing	0.251	N	0.519	neutral	N	0.513909983	None	None	N
R/H	0.0993	likely_benign	0.2248	benign	-1.203	Destabilizing	0.005	N	0.428	neutral	N	0.462481085	None	None	N
R/I	0.4258	ambiguous	0.8048	pathogenic	0.248	Stabilizing	0.38	N	0.574	neutral	None	None	None	None	N
R/K	0.1793	likely_benign	0.2975	benign	-0.581	Destabilizing	0.001	N	0.346	neutral	None	None	None	None	N
R/L	0.3458	ambiguous	0.724	pathogenic	0.248	Stabilizing	0.144	N	0.518	neutral	N	0.442855175	None	None	N
R/M	0.5379	ambiguous	0.8619	pathogenic	-0.135	Destabilizing	0.935	D	0.538	neutral	None	None	None	None	N
R/N	0.6185	likely_pathogenic	0.9043	pathogenic	-0.104	Destabilizing	0.081	N	0.529	neutral	None	None	None	None	N
R/P	0.9519	likely_pathogenic	0.9873	pathogenic	0.009	Stabilizing	0.705	D	0.561	neutral	N	0.46920124	None	None	N
R/Q	0.1399	likely_benign	0.2977	benign	-0.245	Destabilizing	0.38	N	0.572	neutral	None	None	None	None	N
R/S	0.5142	ambiguous	0.8594	pathogenic	-0.769	Destabilizing	0.251	N	0.505	neutral	N	0.447684991	None	None	N
R/T	0.3547	ambiguous	0.745	pathogenic	-0.478	Destabilizing	0.149	N	0.494	neutral	None	None	None	None	N
R/V	0.4488	ambiguous	0.7877	pathogenic	0.009	Stabilizing	0.235	N	0.565	neutral	None	None	None	None	N
R/W	0.3185	likely_benign	0.6698	pathogenic	-0.17	Destabilizing	0.935	D	0.608	neutral	None	None	None	None	N
R/Y	0.4037	ambiguous	0.781	pathogenic	0.145	Stabilizing	0.235	N	0.559	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.