TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22992	69199;69200;69201	chr2:178577361;178577360;178577359	chr2:179442088;179442087;179442086
N2AB	21351	64276;64277;64278	chr2:178577361;178577360;178577359	chr2:179442088;179442087;179442086
N2A	20424	61495;61496;61497	chr2:178577361;178577360;178577359	chr2:179442088;179442087;179442086
N2B	13927	42004;42005;42006	chr2:178577361;178577360;178577359	chr2:179442088;179442087;179442086
Novex-1	14052	42379;42380;42381	chr2:178577361;178577360;178577359	chr2:179442088;179442087;179442086
Novex-2	14119	42580;42581;42582	chr2:178577361;178577360;178577359	chr2:179442088;179442087;179442086
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: Ig-128
• Domain position: 43
• Structural Position: 109
• Q(SASA): 0.6679
• Predicted PPI site: I

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/E	rs755825278	0.01	0.025	N	0.265	0.034	0.104622674875	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
D/G	rs2046668085	None	0.892	N	0.379	0.324	0.16115917748	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	1.3125E-06	0	0
D/Y	None	None	0.056	N	0.461	0.25	0.384086055536	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	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	0.2304	likely_benign	0.2179	benign	0.075	Stabilizing	0.892	D	0.404	neutral	N	0.498652529	None	None	I
D/C	0.7705	likely_pathogenic	0.762	pathogenic	-0.037	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	I
D/E	0.1661	likely_benign	0.1455	benign	-0.348	Destabilizing	0.025	N	0.265	neutral	N	0.469156342	None	None	I
D/F	0.7573	likely_pathogenic	0.727	pathogenic	-0.082	Destabilizing	0.95	D	0.583	neutral	None	None	None	None	I
D/G	0.2446	likely_benign	0.2342	benign	-0.005	Destabilizing	0.892	D	0.379	neutral	N	0.457419195	None	None	I
D/H	0.4331	ambiguous	0.4081	ambiguous	0.464	Stabilizing	0.967	D	0.415	neutral	N	0.463961001	None	None	I
D/I	0.4816	ambiguous	0.436	ambiguous	0.216	Stabilizing	0.975	D	0.582	neutral	None	None	None	None	I
D/K	0.5211	ambiguous	0.488	ambiguous	0.501	Stabilizing	0.95	D	0.385	neutral	None	None	None	None	I
D/L	0.5039	ambiguous	0.4831	ambiguous	0.216	Stabilizing	0.95	D	0.582	neutral	None	None	None	None	I
D/M	0.701	likely_pathogenic	0.6612	pathogenic	0.08	Stabilizing	0.999	D	0.584	neutral	None	None	None	None	I
D/N	0.1447	likely_benign	0.1318	benign	0.291	Stabilizing	0.967	D	0.389	neutral	N	0.487339457	None	None	I
D/P	0.6222	likely_pathogenic	0.604	pathogenic	0.186	Stabilizing	0.987	D	0.399	neutral	None	None	None	None	I
D/Q	0.455	ambiguous	0.4179	ambiguous	0.288	Stabilizing	0.95	D	0.415	neutral	None	None	None	None	I
D/R	0.5714	likely_pathogenic	0.5414	ambiguous	0.617	Stabilizing	0.975	D	0.491	neutral	None	None	None	None	I
D/S	0.1863	likely_benign	0.1735	benign	0.222	Stabilizing	0.916	D	0.345	neutral	None	None	None	None	I
D/T	0.338	likely_benign	0.3091	benign	0.296	Stabilizing	0.975	D	0.413	neutral	None	None	None	None	I
D/V	0.3126	likely_benign	0.2904	benign	0.186	Stabilizing	0.967	D	0.582	neutral	N	0.46446798	None	None	I
D/W	0.9407	likely_pathogenic	0.9395	pathogenic	-0.081	Destabilizing	0.997	D	0.609	neutral	None	None	None	None	I
D/Y	0.3652	ambiguous	0.3535	ambiguous	0.128	Stabilizing	0.056	N	0.461	neutral	N	0.462315159	None	None	I

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.