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Gene-disease assertions not curated here (add link or write note):
Disease | SIM1-related Prader-Willi-like syndrome |
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Inheritance | Autosomal dominant |
Prevalence | <1 / 1 000 000 Source: Orphanet |
Rapid or full curation? | |
ClinGen / GenCC / BabySeq / HGMD / OMIM | No curations for this GDA in ClinGen/GenCC HGMD reports 7 variants in SIM1 associated with Prader-Willi-like syndrome (6 gross deletions and 1 missense from 2 publications) |
Clinical Validity Scoring Notes and points | Variant/Case Evidence: PMID: 25351778 Describes 15 new patients (including 1 fetus) with 6q16 deletions, which is the most common variant in patients exhibiting the PWS-like phenotype Investigated using chromosomal microarray analysis All reported 6q16 deletions occurred de novo in symptomatic patients Other genes also included in these deletions (listed in supplemental information) - unsure if these deletions can be scored
PMID: 26795956 Performed genome-wide microarray analysis on a group of 109 PWL patients, and screened 94 patients for variants in SIM1 and MRAP2 using Sanger sequencing SIM1 analysis resulted in the identification of one rare missense variant (p.P352S) in a 10 year old male clinically diagnosed with PWS although this could not be confirmed molecularly as no aberration on chromosome 15q11.2–q13 was detected with MS-MLPA - 0.5 pts
PMID: 23778136 Identified 4 rare variants (p.I128T, p.Q152E, p.R581G, and p.T714A) in 4 children with Prader-Willi–like syndrome features - 2 pts
PMID: 24038875 De novo interstitial deletion at 6q16.1–q21 (chr6:98,119,288–107,977,239 (hg18)), that included SIM1 and 30 other genes, was identified in a 12 year old male with Prader–Willi-like syndrome - unsure if this deletion can be scored
PMID: 18648397 Report 5 patients with overlapping interstitial 6q16 deletions and Prader–Willi-like phenotype - unsure if these deletions can be scored Cases 2 and 3 show heart defects (ductus arteriosus and atrial septal defects in case 2, tetralogy of Fallot in case 3) and are haploinsufficient for the POPDC3 gene
Segregation Evidence: Case/Control Evidence: Experimental Evidence: PMID: 23778136 Source: |
Clinical Validity Points Total | Source: |
Clinical Validity Classification | Expand |
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| title | Classifications (pts) |
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| Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed |
| Source: |
Molecular Mechanism | Expand |
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| Loss of function Gain of function Dominant negative Unknown Other |
| Loss of function |
Penetrance | Expand |
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| Complete (100%) High (≥80%) Moderate (<80% and >20%) Low (≤20%) |
(list source/PMID) | Source: |
Age of Onset | Expand |
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| Congenital Pediatric Adolescent Adulthood Late adulthood |
(list source/PMID) | |
Severity | Expand |
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| Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete.
Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high.
Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced.
Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low.
None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers. |
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Clinical Features | Sources: |
HPO Terms https://hpo.jax.org/app/ | |
Gene SOPs & Notes | LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant |
Curation Summary | Expand |
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| - The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Variable expression or severity:
The severity and expressivity of the disorder is highly variable, even within families.
- If multiple conditions associated with the gene:
It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited |
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Case ID, Curator name, Date, Jira ticket link | |
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