TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16281	49066;49067;49068	chr2:178614673;178614672;178614671	chr2:179479400;179479399;179479398
N2AB	14640	44143;44144;44145	chr2:178614673;178614672;178614671	chr2:179479400;179479399;179479398
N2A	13713	41362;41363;41364	chr2:178614673;178614672;178614671	chr2:179479400;179479399;179479398
N2B	7216	21871;21872;21873	chr2:178614673;178614672;178614671	chr2:179479400;179479399;179479398
Novex-1	7341	22246;22247;22248	chr2:178614673;178614672;178614671	chr2:179479400;179479399;179479398
Novex-2	7408	22447;22448;22449	chr2:178614673;178614672;178614671	chr2:179479400;179479399;179479398
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-110
• Domain position: 20
• Structural Position: 34
• Q(SASA): 0.165
• 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
T/I	rs1553703631	None	0.473	N	0.631	0.134	0.426670027402	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
T/I	rs1553703631	None	0.473	N	0.631	0.134	0.426670027402	gnomAD-4.0.0	6.58293E-06	None	None	None	None	N	None	0	6.56254E-05	None	0	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
T/A	0.1211	likely_benign	0.0999	benign	-0.188	Destabilizing	0.425	N	0.449	neutral	N	0.465166958	None	None	N
T/C	0.5415	ambiguous	0.4908	ambiguous	-0.296	Destabilizing	0.995	D	0.62	neutral	None	None	None	None	N
T/D	0.5236	ambiguous	0.4325	ambiguous	0.166	Stabilizing	0.007	N	0.35	neutral	None	None	None	None	N
T/E	0.4146	ambiguous	0.3289	benign	0.084	Stabilizing	0.013	N	0.327	neutral	None	None	None	None	N
T/F	0.382	ambiguous	0.3351	benign	-0.738	Destabilizing	0.944	D	0.684	prob.neutral	None	None	None	None	N
T/G	0.4368	ambiguous	0.3773	ambiguous	-0.292	Destabilizing	0.704	D	0.643	neutral	None	None	None	None	N
T/H	0.3802	ambiguous	0.3175	benign	-0.523	Destabilizing	0.944	D	0.665	neutral	None	None	None	None	N
T/I	0.2119	likely_benign	0.184	benign	-0.041	Destabilizing	0.473	N	0.631	neutral	N	0.499009215	None	None	N
T/K	0.3111	likely_benign	0.2493	benign	-0.295	Destabilizing	0.007	N	0.351	neutral	None	None	None	None	N
T/L	0.149	likely_benign	0.1334	benign	-0.041	Destabilizing	0.329	N	0.587	neutral	None	None	None	None	N
T/M	0.1238	likely_benign	0.1053	benign	-0.031	Destabilizing	0.944	D	0.645	neutral	None	None	None	None	N
T/N	0.1967	likely_benign	0.1613	benign	-0.091	Destabilizing	0.642	D	0.512	neutral	N	0.492666247	None	None	N
T/P	0.7257	likely_pathogenic	0.6644	pathogenic	-0.062	Destabilizing	0.784	D	0.679	prob.neutral	N	0.475040877	None	None	N
T/Q	0.3235	likely_benign	0.2606	benign	-0.303	Destabilizing	0.704	D	0.651	neutral	None	None	None	None	N
T/R	0.3151	likely_benign	0.2474	benign	-0.024	Destabilizing	0.007	N	0.503	neutral	None	None	None	None	N
T/S	0.1734	likely_benign	0.1427	benign	-0.274	Destabilizing	0.425	N	0.474	neutral	N	0.465616644	None	None	N
T/V	0.1369	likely_benign	0.1226	benign	-0.062	Destabilizing	0.031	N	0.263	neutral	None	None	None	None	N
T/W	0.7486	likely_pathogenic	0.696	pathogenic	-0.79	Destabilizing	0.995	D	0.672	neutral	None	None	None	None	N
T/Y	0.3985	ambiguous	0.3585	ambiguous	-0.48	Destabilizing	0.981	D	0.685	prob.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.