Submissions for variant NM_003072.5(SMARCA4):c.803_811del (p.Val268_Pro270del)

dbSNP: rs1555754225

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000574724	SCV000664158	uncertain significance	Hereditary cancer-predisposing syndrome	2024-04-19	criteria provided, single submitter	clinical testing	The c.803_811delTGCCCCCCG variant (also known as p.V268_P270del) is located in coding exon 4 of the SMARCA4 gene. This variant results from an in-frame deletion of 9 nucleotides (TGCCCCCCG) at nucleotide positions 803 to 811. This results in the in-frame deletion of 3 amino acids (VPP) at codons 268 to 270. The deleted amino acid positions are well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000646871	SCV000768656	uncertain significance	Rhabdoid tumor predisposition syndrome 2	2024-05-29	criteria provided, single submitter	clinical testing	This variant, c.803_811del, results in the deletion of 3 amino acid(s) of the SMARCA4 protein (p.Val268_Pro270del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 480595). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV001809576	SCV002056358	uncertain significance	Intellectual disability, autosomal dominant 16	2021-07-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000646871	SCV004204916	uncertain significance	Rhabdoid tumor predisposition syndrome 2	2024-03-13	criteria provided, single submitter	clinical testing
GeneDx	RCV004773004	SCV005386639	uncertain significance	not provided	2024-01-16	criteria provided, single submitter	clinical testing	In-frame deletion of 3 amino acids in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV004745483	SCV005355070	uncertain significance	SMARCA4-related disorder	2024-04-12	no assertion criteria provided	clinical testing	The SMARCA4 c.803_811del9 variant is predicted to result in an in-frame deletion (p.Val268_Pro270del). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/480595/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.