Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000990146 | SCV000286145 | benign | Rhabdoid tumor predisposition syndrome 2 | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000766541 | SCV000569850 | uncertain significance | not provided | 2016-09-29 | criteria provided, single submitter | clinical testing | This variant is denoted SMARCA4 c.76G>A at the cDNA level, p.Ala26Thr (A26T) at the protein level, and results in the change of an Alanine to a Threonine (GCC>ACC). This variant was identified in 1/236 healthy Hispanic individuals undergoing whole genome sequencing (Bodian 2014). Of note, the participants in this study were younger than 50 years old thus the unaffected status of this individual may not be significant. SMARCA4 Ala26Thr was observed with an allele frequency of 0.3% (12/4378) in African Americans in the NHLBI Exome Sequencing Project. Since Alanine and Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. SMARCA4 Ala26Thr occurs at a position that is conserved in mammals and is located within the region of interaction with SS18L1/CREST (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether SMARCA4 Ala26Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000566087 | SCV000663893 | likely benign | Hereditary cancer-predisposing syndrome | 2019-03-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Mendelics | RCV000990146 | SCV001140974 | likely benign | Rhabdoid tumor predisposition syndrome 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001808347 | SCV002057817 | likely benign | Intellectual disability, autosomal dominant 16 | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000566087 | SCV002535237 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-08 | criteria provided, single submitter | curation | |
Prevention |
RCV003925210 | SCV004738347 | likely benign | SMARCA4-related disorder | 2019-09-26 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
ITMI | RCV000122060 | SCV000086271 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |